rs1268762655
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate
The ENST00000295550.9(COL6A3):c.6853G>A(p.Gly2285Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,614,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. G2285G) has been classified as Benign.
Frequency
Consequence
ENST00000295550.9 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL6A3 | NM_004369.4 | c.6853G>A | p.Gly2285Arg | missense_variant | 28/44 | ENST00000295550.9 | NP_004360.2 | |
COL6A3 | NM_057167.4 | c.6235G>A | p.Gly2079Arg | missense_variant | 27/43 | NP_476508.2 | ||
COL6A3 | NM_057166.5 | c.5032G>A | p.Gly1678Arg | missense_variant | 25/41 | NP_476507.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL6A3 | ENST00000295550.9 | c.6853G>A | p.Gly2285Arg | missense_variant | 28/44 | 1 | NM_004369.4 | ENSP00000295550 | P1 | |
COL6A3 | ENST00000472056.5 | c.5032G>A | p.Gly1678Arg | missense_variant | 25/41 | 1 | ENSP00000418285 | |||
COL6A3 | ENST00000353578.9 | c.6235G>A | p.Gly2079Arg | missense_variant | 27/43 | 5 | ENSP00000315873 | |||
COL6A3 | ENST00000491769.1 | n.1107G>A | non_coding_transcript_exon_variant | 5/20 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152168Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461848Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 727218
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152168Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74340
ClinVar
Submissions by phenotype
Bethlem myopathy 1A Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 20, 2018 | In summary, this variant is novel missense change that affects a functionally critical residue. This evidence indicates that it is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Glycine residues within the triple helix region are crucial to maintain fibrillar collagens structure and stability (PMID: 7695699, 19344236). In the case of COL6A3, missense substitutions that affect glycine residues within the triplex helix domain have been reported in many patients affected with collagen VI myopathy (PMID: 24038877). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a COL6A3-related disease. This sequence change replaces glycine with arginine at codon 2285 of the COL6A3 protein (p.Gly2285Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at