chr2-237365784-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004369.4(COL6A3):c.5752C>T(p.Arg1918Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,614,088 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1918H) has been classified as Likely benign.
Frequency
Consequence
NM_004369.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A3 | NM_004369.4 | c.5752C>T | p.Arg1918Cys | missense_variant | 12/44 | ENST00000295550.9 | |
COL6A3 | NM_057167.4 | c.5134C>T | p.Arg1712Cys | missense_variant | 11/43 | ||
COL6A3 | NM_057166.5 | c.3931C>T | p.Arg1311Cys | missense_variant | 9/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A3 | ENST00000295550.9 | c.5752C>T | p.Arg1918Cys | missense_variant | 12/44 | 1 | NM_004369.4 | P1 | |
COL6A3 | ENST00000472056.5 | c.3931C>T | p.Arg1311Cys | missense_variant | 9/41 | 1 | |||
COL6A3 | ENST00000353578.9 | c.5134C>T | p.Arg1712Cys | missense_variant | 11/43 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152198Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251444Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135902
GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461890Hom.: 0 Cov.: 32 AF XY: 0.0000179 AC XY: 13AN XY: 727246
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152198Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74356
ClinVar
Submissions by phenotype
Bethlem myopathy 1A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 14, 2023 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1918 of the COL6A3 protein (p.Arg1918Cys). This variant is present in population databases (rs750367811, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with COL6A3-related conditions. 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) performed at Invitae indicates that this missense variant is not expected to disrupt COL6A3 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at