rs373948031
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_ModerateBP6BP7
The NM_001848.3(COL6A1):c.993C>T(p.Asp331=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000587 in 1,074,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00059 ( 0 hom., cov: 0)
Exomes 𝑓: 0.000050 ( 0 hom. )
Consequence
COL6A1
NM_001848.3 synonymous
NM_001848.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.569
Genes affected
COL6A1 (HGNC:2211): (collagen type VI alpha 1 chain) The collagens are a superfamily of proteins that play a role in maintaining the integrity of various tissues. Collagens are extracellular matrix proteins and have a triple-helical domain as their common structural element. Collagen VI is a major structural component of microfibrils. The basic structural unit of collagen VI is a heterotrimer of the alpha1(VI), alpha2(VI), and alpha3(VI) chains. The alpha2(VI) and alpha3(VI) chains are encoded by the COL6A2 and COL6A3 genes, respectively. The protein encoded by this gene is the alpha 1 subunit of type VI collagen (alpha1(VI) chain). Mutations in the genes that code for the collagen VI subunits result in the autosomal dominant disorder, Bethlem myopathy. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.37).
BP6
Variant 21-45990413-C-T is Benign according to our data. Variant chr21-45990413-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 258312.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=-0.569 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL6A1 | NM_001848.3 | c.993C>T | p.Asp331= | synonymous_variant | 13/35 | ENST00000361866.8 | NP_001839.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL6A1 | ENST00000361866.8 | c.993C>T | p.Asp331= | synonymous_variant | 13/35 | 1 | NM_001848.3 | ENSP00000355180 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000589 AC: 10AN: 16968Hom.: 0 Cov.: 0
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GnomAD3 exomes AF: 0.0000836 AC: 17AN: 203458Hom.: 1 AF XY: 0.0000891 AC XY: 10AN XY: 112296
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GnomAD4 exome AF: 0.0000501 AC: 53AN: 1057032Hom.: 0 Cov.: 49 AF XY: 0.0000465 AC XY: 24AN XY: 516504
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GnomAD4 genome AF: 0.000588 AC: 10AN: 17000Hom.: 0 Cov.: 0 AF XY: 0.000986 AC XY: 8AN XY: 8114
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 17, 2015 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Bethlem myopathy 1A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 06, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
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DANN
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at