rs387907150
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 14P and 1B. PM1PM2PM5PP5_Very_StrongBP4
The NM_058246.4(DNAJB6):c.265T>A(p.Phe89Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F89L) has been classified as Likely pathogenic.
Frequency
Consequence
NM_058246.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAJB6 | NM_058246.4 | c.265T>A | p.Phe89Ile | missense_variant | 5/10 | ENST00000262177.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAJB6 | ENST00000262177.9 | c.265T>A | p.Phe89Ile | missense_variant | 5/10 | 1 | NM_058246.4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152272Hom.: 0 Cov.: 33
GnomAD4 exome Cov.: 29
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152272Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74390
ClinVar
Submissions by phenotype
Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6) Pathogenic:4
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 16, 2023 | 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. - |
Pathogenic, criteria provided, single submitter | research | Baylor-Hopkins Center for Mendelian Genomics, Johns Hopkins University School of Medicine | - | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | May 01, 2014 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Aug 22, 2022 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 14, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at