rs148183839
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_004369.4(COL6A3):c.9524T>C(p.Met3175Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00084 in 1,613,868 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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. M3175L) has been classified as Likely benign.
Frequency
Consequence
NM_004369.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A3 | NM_004369.4 | c.9524T>C | p.Met3175Thr | missense_variant | 44/44 | ENST00000295550.9 | |
COL6A3 | NM_057167.4 | c.8906T>C | p.Met2969Thr | missense_variant | 43/43 | ||
COL6A3 | NM_057166.5 | c.7703T>C | p.Met2568Thr | missense_variant | 41/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A3 | ENST00000295550.9 | c.9524T>C | p.Met3175Thr | missense_variant | 44/44 | 1 | NM_004369.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00101 AC: 154AN: 152170Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00114 AC: 285AN: 248940Hom.: 1 AF XY: 0.00110 AC XY: 148AN XY: 134712
GnomAD4 exome AF: 0.000822 AC: 1202AN: 1461580Hom.: 2 Cov.: 31 AF XY: 0.000811 AC XY: 590AN XY: 727078
GnomAD4 genome ? AF: 0.00101 AC: 154AN: 152288Hom.: 0 Cov.: 32 AF XY: 0.00134 AC XY: 100AN XY: 74464
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Nov 08, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 12, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2023 | COL6A3: BS1 - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 01, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital | Oct 05, 2017 | BS1,BP6; This alteration has an allele frequency that is greater than expected for the associated disease, and was reported as a benign/likely benign alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory). - |
COL6A3-related condition Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 22, 2023 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
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. - |
Bethlem myopathy 1A Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at