ClinVar Genomic variation as it relates to human health
NM_058246.4(DNAJB6):c.265T>A (p.Phe89Ile)
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_058246.4(DNAJB6):c.265T>A (p.Phe89Ile)
Variation ID: 31531 Accession: VCV000031531.16
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7q36.3 7: 157367402 (GRCh38) [ NCBI UCSC ] 7: 157160096 (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 Feb 20, 2024 Aug 16, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_058246.4:c.265T>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_490647.1:p.Phe89Ile missense NM_001363676.1:c.265T>A NP_001350605.1:p.Phe89Ile missense NM_005494.3:c.265T>A NP_005485.1:p.Phe89Ile missense NC_000007.14:g.157367402T>A NC_000007.13:g.157160096T>A NG_032573.1:g.35387T>A O75190:p.Phe89Ile - Protein change
- F89I
- Other names
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- Canonical SPDI
- NC_000007.14:157367401:T:A
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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) 0.00001
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
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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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DNAJB6 | No evidence available | No evidence available |
GRCh38 GRCh37 |
439 | 530 |
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 (4) |
criteria provided, multiple submitters, no conflicts
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Aug 16, 2023 | RCV000024242.21 | |
Pathogenic (1) |
criteria provided, single submitter
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Nov 14, 2017 | RCV000724639.4 |
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
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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
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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
(Nov 14, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000331805.4
First in ClinVar: Dec 06, 2016 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 37
Sex: mixed
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Pathogenic
(-)
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criteria provided, single submitter
Method: research
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Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
somatic
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Baylor-Hopkins Center for Mendelian Genomics, Johns Hopkins University School of Medicine
Accession: SCV001425534.1
First in ClinVar: Aug 01, 2020 Last updated: Aug 01, 2020 |
Number of individuals with the variant: 4
Family history: yes
Geographic origin: European
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Pathogenic
(Aug 22, 2022)
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criteria provided, single submitter
Method: clinical testing
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Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002021724.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Aug 16, 2023)
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criteria provided, single submitter
Method: clinical testing
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Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000649789.7
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces phenylalanine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 89 of the DNAJB6 protein (p.Phe89Ile). … (more)
This sequence change replaces phenylalanine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 89 of the DNAJB6 protein (p.Phe89Ile). This variant is present in population databases (rs387907150, gnomAD 0.007%). This missense change has been observed in individual(s) with limb girdle muscular dystrophy type 1D (PMID: 22366786, 24594375). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 31531). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DNAJB6 protein function. Experimental studies have shown that this missense change affects DNAJB6 function (PMID: 22366786, 24920671, 26371419). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(May 01, 2014)
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no assertion criteria provided
Method: literature only
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MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL DOMINANT 1
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000045533.5
First in ClinVar: Apr 04, 2013 Last updated: Aug 15, 2022 |
Comment on evidence:
In affected members of 2 families from the U.S. with limb-girdle muscular dystrophy type 1E (LGMDD1; 603511), originally reported by Speer et al. (1995, 1999), … (more)
In affected members of 2 families from the U.S. with limb-girdle muscular dystrophy type 1E (LGMDD1; 603511), originally reported by Speer et al. (1995, 1999), Sarparanta et al. (2012) identified a heterozygous c.265T-A transversion (which they referred to as c.267T-A) in the DNAJB6 gene, resulting in a phe89-to-ile (F89I) substitution at a highly conserved residue in the G/F domain. The mutation was not found in 202 Finnish, 104 Italian, or 215 U.S. control individuals. In affected members of an American family with LGMD1E, Couthouis et al. (2014) identified a heterozygous c.265T-A transversion in the DNAJB6 gene, resulting in a phe89-to-ile (F89I) substitution. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder. It was filtered against the dbSNP (build 137), 1000 Genomes Project, and Exome Sequencing project databases. Couthouis et al. (2014) stated that the mutation was the same as that identified by Sarparanta et al. (2012). Haplotype analysis determined that the mutation arose independently in the families reported by Couthouis et al. (2014) and Sarparanta et al. (2012), suggesting that it may be a mutation hotspot. Functional studies of the variant were not performed. (less)
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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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Myopathy-causing mutations in an HSP40 chaperone disrupt processing of specific client conformers. | Stein KC | The Journal of biological chemistry | 2014 | PMID: 24920671 |
Exome sequencing identifies a DNAJB6 mutation in a family with dominantly-inherited limb-girdle muscular dystrophy. | Couthouis J | Neuromuscular disorders : NMD | 2014 | PMID: 24594375 |
Mutations affecting the cytoplasmic functions of the co-chaperone DNAJB6 cause limb-girdle muscular dystrophy. | Sarparanta J | Nature genetics | 2012 | PMID: 22366786 |
Identification of a new autosomal dominant limb-girdle muscular dystrophy locus on chromosome 7. | Speer MC | American journal of human genetics | 1999 | PMID: 9973293 |
Evidence for locus heterogeneity in autosomal dominant limb-girdle muscular dystrophy. | Speer MC | American journal of human genetics | 1995 | PMID: 8533766 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=DNAJB6 | - | - | - | - |
Text-mined citations for rs387907150 ...
HelpRecord last updated Apr 15, 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.