chr2-237369032-G-A
Variant names:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_004369.4(COL6A3):c.4431C>T(p.Val1477Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,614,162 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 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000017 ( 0 hom. )
Consequence
COL6A3
NM_004369.4 synonymous
NM_004369.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.92
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=-0.71).
BP6
Variant 2-237369032-G-A is Benign according to our data. Variant chr2-237369032-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 288088.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=-1.91 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| COL6A3 | NM_004369.4 | c.4431C>T | p.Val1477Val | synonymous_variant | Exon 10 of 44 | ENST00000295550.9 | NP_004360.2 | |
| COL6A3 | NM_057167.4 | c.3813C>T | p.Val1271Val | synonymous_variant | Exon 9 of 43 | NP_476508.2 | ||
| COL6A3 | NM_057166.5 | c.2610C>T | p.Val870Val | synonymous_variant | Exon 7 of 41 | NP_476507.3 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| COL6A3 | ENST00000295550.9 | c.4431C>T | p.Val1477Val | synonymous_variant | Exon 10 of 44 | 1 | NM_004369.4 | ENSP00000295550.4 | ||
| COL6A3 | ENST00000472056.5 | c.2610C>T | p.Val870Val | synonymous_variant | Exon 7 of 41 | 1 | ENSP00000418285.1 | |||
| COL6A3 | ENST00000353578.9 | c.3813C>T | p.Val1271Val | synonymous_variant | Exon 9 of 43 | 5 | ENSP00000315873.4 | |||
| COL6A3 | ENST00000684597.1 | c.116-356C>T | intron_variant | Intron 1 of 2 | ENSP00000508021.1 |
Frequencies
GnomAD3 genomes 0.0000394 AC: 6AN: 152160Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251310Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135844
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GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461884Hom.: 0 Cov.: 37 AF XY: 0.0000124 AC XY: 9AN XY: 727244
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GnomAD4 genome 0.0000394 AC: 6AN: 152278Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74452
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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
May 12, 2016
Eurofins Ntd Llc (ga)
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Bethlem myopathy 1A Benign:1
Mar 09, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
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