2-237324814-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004369.4(COL6A3):āc.9494T>Gā(p.Val3165Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,232 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_004369.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A3 | NM_004369.4 | c.9494T>G | p.Val3165Gly | missense_variant, splice_region_variant | 44/44 | ENST00000295550.9 | |
COL6A3 | NM_057167.4 | c.8876T>G | p.Val2959Gly | missense_variant, splice_region_variant | 43/43 | ||
COL6A3 | NM_057166.5 | c.7673T>G | p.Val2558Gly | missense_variant, splice_region_variant | 41/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A3 | ENST00000295550.9 | c.9494T>G | p.Val3165Gly | missense_variant, splice_region_variant | 44/44 | 1 | NM_004369.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 248064Hom.: 0 AF XY: 0.00000745 AC XY: 1AN XY: 134260
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461232Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726872
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Bethlem myopathy 1A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 12, 2022 | This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 3165 of the COL6A3 protein (p.Val3165Gly). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with COL6A3-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0". The glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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