rs375729592
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_004369.4(COL6A3):c.7113C>T(p.Gly2371=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000663 in 1,614,142 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 0.00024 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000049 ( 0 hom. )
Consequence
COL6A3
NM_004369.4 synonymous
NM_004369.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.633
Genes affected
COL6A3 (HGNC:2213): (collagen type VI alpha 3 chain) This gene encodes the alpha-3 chain, one of the three alpha chains of type VI collagen, a beaded filament collagen found in most connective tissues. The alpha-3 chain of type VI collagen is much larger than the alpha-1 and -2 chains. This difference in size is largely due to an increase in the number of subdomains, similar to von Willebrand Factor type A domains, that are found in the amino terminal globular domain of all the alpha chains. These domains have been shown to bind extracellular matrix proteins, an interaction that explains the importance of this collagen in organizing matrix components. Mutations in the type VI collagen genes are associated with Bethlem myopathy, a rare autosomal dominant proximal myopathy with early childhood onset. Mutations in this gene are also a cause of Ullrich congenital muscular dystrophy, also referred to as Ullrich scleroatonic muscular dystrophy, an autosomal recessive congenital myopathy that is more severe than Bethlem myopathy. Multiple transcript variants have been identified, but the full-length nature of only some of these variants has been described. [provided by RefSeq, Jun 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 2-237345193-G-A is Benign according to our data. Variant chr2-237345193-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 282483.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=-0.633 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| COL6A3 | NM_004369.4 | c.7113C>T | p.Gly2371= | synonymous_variant | 33/44 | ENST00000295550.9 | NP_004360.2 | |
| COL6A3 | NM_057167.4 | c.6495C>T | p.Gly2165= | synonymous_variant | 32/43 | NP_476508.2 | ||
| COL6A3 | NM_057166.5 | c.5292C>T | p.Gly1764= | synonymous_variant | 30/41 | NP_476507.3 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| COL6A3 | ENST00000295550.9 | c.7113C>T | p.Gly2371= | synonymous_variant | 33/44 | 1 | NM_004369.4 | ENSP00000295550 | P1 | |
| COL6A3 | ENST00000472056.5 | c.5292C>T | p.Gly1764= | synonymous_variant | 30/41 | 1 | ENSP00000418285 | |||
| COL6A3 | ENST00000353578.9 | c.6495C>T | p.Gly2165= | synonymous_variant | 32/43 | 5 | ENSP00000315873 | |||
| COL6A3 | ENST00000491769.1 | n.1367C>T | non_coding_transcript_exon_variant | 10/20 | 5 |
Frequencies
GnomAD3 genomes 0.000237 AC: 36AN: 152154Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000955 AC: 24AN: 251192Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135810
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GnomAD4 exome AF: 0.0000486 AC: 71AN: 1461870Hom.: 0 Cov.: 33 AF XY: 0.0000536 AC XY: 39AN XY: 727232
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GnomAD4 genome 0.000236 AC: 36AN: 152272Hom.: 0 Cov.: 32 AF XY: 0.000282 AC XY: 21AN XY: 74446
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
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) | Jun 15, 2017 | - - |
Bethlem myopathy 1A Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 18, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
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DANN
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at