rs138285547
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_004369.4(COL6A3):c.7849G>A(p.Asp2617Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000136 in 1,614,166 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D2617E) has been classified as Uncertain significance.
Frequency
Consequence
NM_004369.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A3 | NM_004369.4 | c.7849G>A | p.Asp2617Asn | missense_variant | 38/44 | ENST00000295550.9 | |
COL6A3 | NM_057167.4 | c.7231G>A | p.Asp2411Asn | missense_variant | 37/43 | ||
COL6A3 | NM_057166.5 | c.6028G>A | p.Asp2010Asn | missense_variant | 35/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A3 | ENST00000295550.9 | c.7849G>A | p.Asp2617Asn | missense_variant | 38/44 | 1 | NM_004369.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000664 AC: 101AN: 152192Hom.: 1 Cov.: 31
GnomAD3 exomes AF: 0.000200 AC: 50AN: 250624Hom.: 1 AF XY: 0.000111 AC XY: 15AN XY: 135454
GnomAD4 exome AF: 0.0000807 AC: 118AN: 1461856Hom.: 0 Cov.: 35 AF XY: 0.0000591 AC XY: 43AN XY: 727226
GnomAD4 genome ? AF: 0.000663 AC: 101AN: 152310Hom.: 1 Cov.: 31 AF XY: 0.000645 AC XY: 48AN XY: 74474
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | May 30, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 26, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 20, 2020 | - - |
Bethlem myopathy 1A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
Collagen 6-related myopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
COL6A3-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 22, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at