rs121912936
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PM1PM2PP3_StrongPP5_Very_Strong
The NM_001848.3(COL6A1):c.362A>G(p.Lys121Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Consequence
NM_001848.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL6A1 | NM_001848.3 | c.362A>G | p.Lys121Arg | missense_variant | Exon 3 of 35 | ENST00000361866.8 | NP_001839.2 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 35
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1460338Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 726494
GnomAD4 genome Cov.: 35
ClinVar
Submissions by phenotype
Bethlem myopathy 1A Pathogenic:2
This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 121 of the COL6A1 protein (p.Lys121Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of autosomal dominant type VI collagenopathies (PMID: 11865138, 28877744; internal data). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 17173). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt COL6A1 protein function with a negative predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. -
- -
not provided Pathogenic:2
- -
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at