rs746277006
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_004369.4(COL6A3):āc.1204G>Cā(p.Val402Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_004369.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A3 | NM_004369.4 | c.1204G>C | p.Val402Leu | missense_variant | 4/44 | ENST00000295550.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A3 | ENST00000295550.9 | c.1204G>C | p.Val402Leu | missense_variant | 4/44 | 1 | NM_004369.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 250820Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135572
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461670Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727112
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Bethlem myopathy 1A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 07, 2021 | In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. This variant is present in population databases (rs746277006, ExAC 0.009%) but has not been reported in the literature in individuals with a COL6A3-related disease. This sequence change replaces valine with leucine at codon 402 of the COL6A3 protein (p.Val402Leu). The valine residue is weakly conserved and there is a small physicochemical difference between valine and leucine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at