ClinVar Genomic variation as it relates to human health
NM_000341.4(SLC3A1):c.808C>T (p.Arg270Ter)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000341.4(SLC3A1):c.808C>T (p.Arg270Ter)
Variation ID: 336195 Accession: VCV000336195.23
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2p21 2: 44286074 (GRCh38) [ NCBI UCSC ] 2: 44513213 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Dec 6, 2016 May 12, 2024 Nov 27, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000341.4:c.808C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000332.2:p.Arg270Ter nonsense NC_000002.12:g.44286074C>T NC_000002.11:g.44513213C>T NG_008233.1:g.15617C>T - Protein change
- R270*
- Other names
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- Canonical SPDI
- NC_000002.12:44286073:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00019
Trans-Omics for Precision Medicine (TOPMed) 0.00019
Exome Aggregation Consortium (ExAC) 0.00022
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00023
The Genome Aggregation Database (gnomAD), exomes 0.00039
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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SLC3A1 | - | - |
GRCh38 GRCh37 |
300 | 483 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Nov 27, 2023 | RCV000332132.14 | |
Pathogenic (3) |
criteria provided, single submitter
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Nov 1, 2023 | RCV001723928.7 | |
Pathogenic (1) |
no assertion criteria provided
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Jul 28, 2023 | RCV003313951.3 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Apr 28, 2017)
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criteria provided, single submitter
Method: clinical testing
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Cystinuria
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000430661.3
First in ClinVar: Dec 06, 2016 Last updated: May 24, 2019 |
Comment:
The SLC3A1 c.808C>T (p.Arg270Ter) variant has been reported in at least 11 individuals with cystinuria, including two siblings, in a homozygous state, and one individual … (more)
The SLC3A1 c.808C>T (p.Arg270Ter) variant has been reported in at least 11 individuals with cystinuria, including two siblings, in a homozygous state, and one individual in a compound heterozygous state (Pras et al. 1995; Endsley et al. 1997; Gitomet et al. 1998; Botzenhart et al. 2002; Chatzikyriakidou et al. 2005; Merieau et al. 2009). Four of the individuals homozygous for the p.Arg270Ter variant were of Ashkenazi Jewish ancestry (Pras et al. 1995). Control data are not available for the variant which is reported at a frequency of 0.00041 in the European (non-Finnish) population of the Exome Aggregation Consortium database. Based on the evidence and due to the potential impact of stop-gained variants, the p.Arg270Ter variant is classified as pathogenic for cystinuria. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
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Pathogenic
(Feb 16, 2022)
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criteria provided, single submitter
Method: clinical testing
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Cystinuria
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002811499.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Jan 25, 2022)
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criteria provided, single submitter
Method: clinical testing
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Cystinuria
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV003821219.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Pathogenic
(Nov 27, 2023)
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criteria provided, single submitter
Method: clinical testing
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Cystinuria
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001208284.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg270*) in the SLC3A1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Arg270*) in the SLC3A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC3A1 are known to be pathogenic (PMID: 24610330, 25109415, 25964309). This variant is present in population databases (rs200483989, gnomAD 0.8%). This premature translational stop signal has been observed in individuals with cystinuria (PMID: 7539209, 28646536). ClinVar contains an entry for this variant (Variation ID: 336195). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Nov 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV004183738.4
First in ClinVar: Dec 24, 2023 Last updated: May 12, 2024 |
Comment:
SLC3A1: PVS1, PM2
Number of individuals with the variant: 1
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Pathogenic
(Jan 06, 2020)
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no assertion criteria provided
Method: curation
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Cystinuria
Affected status: unknown
Allele origin:
germline
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Reproductive Health Research and Development, BGI Genomics
Accession: SCV001142317.1
First in ClinVar: Jan 13, 2020 Last updated: Jan 13, 2020 |
Comment:
NM_000341.3:c.808C>T in the SLC3A1 gene has an allele frequency of 0.009 in Ashkenazi Jewish subpopulation in the gnomAD database. This variant is predicted to cause … (more)
NM_000341.3:c.808C>T in the SLC3A1 gene has an allele frequency of 0.009 in Ashkenazi Jewish subpopulation in the gnomAD database. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Botzenhart E et al. identified this variant in two patients with cystinuria, including one in homozygous state amd one in compound heterozygous state (R270X/M467T) (PMID: 12234283 ). Gitomer WL et al. found this mutation in 3 patients in homozygous status, two were siblings (PMID: 9768685). Taken together, we interprete this variant as Pathogenic/Likely pathogenic. ACMG/AMP Criteria applied: PVS1, PM3_Strong, PP4. (less)
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001957161.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001969701.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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Pathogenic
(Jul 28, 2023)
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no assertion criteria provided
Method: clinical testing
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Autism spectrum disorder
Affected status: yes
Allele origin:
unknown
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Gene Friend Way, National Innovation Center
Accession: SCV004013895.2
First in ClinVar: Jul 22, 2023 Last updated: Aug 30, 2023 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg270*) in the SLC3A1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Arg270*) in the SLC3A1 gene. It is expected to result in an absent or disrupted protein product which can manifest as kidney disease. In autism, there have been studies that show a link between ASD and kidney disease. PMID: 33340339. Mutations in SLC3A1 are known as the causative factor of cystinuria, which involving the defective transepithelial transport of cystine and the ability to reabsorb cystine into the blood (PMID: 25109415, 25964309). Meanwhile, plasma concentration of cystein is significantly decreased in ASD children (PMID: 15585776). In our study, an ASD patient carries this SLC3A1 rs200483989 mutation. (less)
Number of individuals with the variant: 1
Method: 800K direct targets snp array, validated with Sanger sequencing
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Spectrum of mutations in cystinuria patients presenting with prenatal hyperechoic colon. | Tostivint I | Clinical genetics | 2017 | PMID: 28646536 |
Clinical and genetic analysis of patients with cystinuria in the United Kingdom. | Rhodes HL | Clinical journal of the American Society of Nephrology : CJASN | 2015 | PMID: 25964309 |
The genetic diversity of cystinuria in a UK population of patients. | Wong KA | BJU international | 2015 | PMID: 25109415 |
PREPL deficiency with or without cystinuria causes a novel myasthenic syndrome. | Régal L | Neurology | 2014 | PMID: 24610330 |
An antenatal hyper-echogenic colon: question. | Merieau E | Pediatric nephrology (Berlin, Germany) | 2009 | PMID: 18704508 |
Identification of novel cystinuria mutations and polymorphisms in SLC3A1 and SLC7A9 genes: absence of SLC7A10 gene mutations in cystinuric patients. | Chatzikyriakidou A | Genetic testing | 2005 | PMID: 16225397 |
Cystinuria in children: distribution and frequencies of mutations in the SLC3A1 and SLC7A9 genes. | Botzenhart E | Kidney international | 2002 | PMID: 12234283 |
Mutations in the genomic deoxyribonucleic acid for SLC3A1 in patients with cystinuria. | Gitomer WL | The Journal of clinical endocrinology and metabolism | 1998 | PMID: 9768685 |
Genomic organization of a human cystine transporter gene (SLC3A1) and identification of novel mutations causing cystinuria. | Endsley JK | Kidney international | 1997 | PMID: 9186880 |
Mutations in the SLC3A1 transporter gene in cystinuria. | Pras E | American journal of human genetics | 1995 | PMID: 7539209 |
Text-mined citations for rs200483989 ...
HelpRecord last updated May 12, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.