rs781087176
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004369.4(COL6A3):āc.7311C>Gā(p.Ser2437Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,607,878 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S2437N) has been classified as Uncertain significance.
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.7311C>G | p.Ser2437Arg | missense_variant | 36/44 | ENST00000295550.9 | |
COL6A3 | NM_057167.4 | c.6693C>G | p.Ser2231Arg | missense_variant | 35/43 | ||
COL6A3 | NM_057166.5 | c.5490C>G | p.Ser1830Arg | missense_variant | 33/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A3 | ENST00000295550.9 | c.7311C>G | p.Ser2437Arg | missense_variant | 36/44 | 1 | NM_004369.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152160Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000810 AC: 2AN: 246830Hom.: 0 AF XY: 0.00000748 AC XY: 1AN XY: 133684
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1455718Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1AN XY: 723580
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152160Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74328
ClinVar
Submissions by phenotype
Bethlem myopathy 1A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 16, 2017 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with COL6A3-related disease. This variant is present in population databases (rs781087176, ExAC 0.002%). This sequence change replaces serine with arginine at codon 2437 of the COL6A3 protein (p.Ser2437Arg). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and arginine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at