rs540633944
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_004369.4(COL6A3):āc.6452T>Cā(p.Val2151Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,614,106 control chromosomes in the GnomAD database, including 2 homozygotes. 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V2151L) has been classified as Uncertain significance.
Frequency
Consequence
NM_004369.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A3 | NM_004369.4 | c.6452T>C | p.Val2151Ala | missense_variant | 21/44 | ENST00000295550.9 | |
COL6A3 | NM_057167.4 | c.5834T>C | p.Val1945Ala | missense_variant | 20/43 | ||
COL6A3 | NM_057166.5 | c.4631T>C | p.Val1544Ala | missense_variant | 18/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A3 | ENST00000295550.9 | c.6452T>C | p.Val2151Ala | missense_variant | 21/44 | 1 | NM_004369.4 | P1 | |
COL6A3 | ENST00000472056.5 | c.4631T>C | p.Val1544Ala | missense_variant | 18/41 | 1 | |||
COL6A3 | ENST00000353578.9 | c.5834T>C | p.Val1945Ala | missense_variant | 20/43 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152198Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251470Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135908
GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461790Hom.: 2 Cov.: 31 AF XY: 0.0000220 AC XY: 16AN XY: 727202
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152316Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4AN XY: 74498
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 25, 2020 | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Bethlem myopathy 1A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at