rs560225578
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The ENST00000295550.9(COL6A3):c.6528C>T(p.Leu2176=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,614,080 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000021 ( 0 hom. )
Consequence
COL6A3
ENST00000295550.9 synonymous
ENST00000295550.9 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.00600
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 Benign. Variant got -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
Variant 2-237357826-G-A is Benign according to our data. Variant chr2-237357826-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 543016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.006 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL6A3 | NM_004369.4 | c.6528C>T | p.Leu2176= | synonymous_variant | 22/44 | ENST00000295550.9 | NP_004360.2 | |
COL6A3 | NM_057167.4 | c.5910C>T | p.Leu1970= | synonymous_variant | 21/43 | NP_476508.2 | ||
COL6A3 | NM_057166.5 | c.4707C>T | p.Leu1569= | synonymous_variant | 19/41 | NP_476507.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL6A3 | ENST00000295550.9 | c.6528C>T | p.Leu2176= | synonymous_variant | 22/44 | 1 | NM_004369.4 | ENSP00000295550 | P1 | |
COL6A3 | ENST00000472056.5 | c.4707C>T | p.Leu1569= | synonymous_variant | 19/41 | 1 | ENSP00000418285 | |||
COL6A3 | ENST00000353578.9 | c.5910C>T | p.Leu1970= | synonymous_variant | 21/43 | 5 | ENSP00000315873 | |||
COL6A3 | ENST00000493475.2 | n.58C>T | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152182Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251478Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135914
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GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461780Hom.: 0 Cov.: 32 AF XY: 0.0000275 AC XY: 20AN XY: 727196
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152300Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74466
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Bethlem myopathy 1A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 18, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2022 | COL6A3: BP4, BP7 - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
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