rs890268146
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004369.4(COL6A3):c.7948G>A(p.Asp2650Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000821 in 1,461,862 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. D2650G) 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.7948G>A | p.Asp2650Asn | missense_variant | 38/44 | ENST00000295550.9 | |
COL6A3 | NM_057167.4 | c.7330G>A | p.Asp2444Asn | missense_variant | 37/43 | ||
COL6A3 | NM_057166.5 | c.6127G>A | p.Asp2043Asn | missense_variant | 35/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A3 | ENST00000295550.9 | c.7948G>A | p.Asp2650Asn | missense_variant | 38/44 | 1 | NM_004369.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461862Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5AN XY: 727236
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Bethlem myopathy 1A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 24, 2016 | In summary, this variant is a novel missense change with uncertain impact on protein function. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a COL6A3-related disease. This sequence change replaces aspartic acid with asparagine at codon 2650 of the COL6A3 protein (p.Asp2650Asn). The aspartic acid residue is weakly conserved and there is a small physicochemical difference between aspartic acid and asparagine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at