NM_004369.4:c.1575G>A
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_ModerateBP6_ModerateBP7
The NM_004369.4(COL6A3):c.1575G>A(p.Thr525Thr) 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 1,614,112 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: 0.000019 ( 0 hom. )
Consequence
COL6A3
NM_004369.4 synonymous
NM_004369.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.521
Publications
1 publications found
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]
COL6A3 Gene-Disease associations (from GenCC):
- Bethlem myopathy 1AInheritance: AD, AR, SD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Ambry Genetics
- collagen 6-related myopathyInheritance: AD, AR Classification: DEFINITIVE Submitted by: ClinGen
- Ullrich congenital muscular dystrophy 1CInheritance: AR Classification: DEFINITIVE Submitted by: G2P
- dystonia 27Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED, NO_KNOWN Submitted by: Illumina, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Orphanet
- Ullrich congenital muscular dystrophy 1AInheritance: AR, AD, SD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
- Bethlem myopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Ullrich congenital muscular dystrophyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -5 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
Variant 2-237381237-C-T is Benign according to our data. Variant chr2-237381237-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 567858.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.521 with no splicing effect.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152218Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
3
AN:
152218
Hom.:
Cov.:
33
Gnomad AFR
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GnomAD2 exomes AF: 0.00000796 AC: 2AN: 251392 AF XY: 0.00000736 show subpopulations
GnomAD2 exomes
AF:
AC:
2
AN:
251392
AF XY:
Gnomad AFR exome
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GnomAD4 exome AF: 0.0000192 AC: 28AN: 1461894Hom.: 0 Cov.: 32 AF XY: 0.0000206 AC XY: 15AN XY: 727248 show subpopulations
GnomAD4 exome
AF:
AC:
28
AN:
1461894
Hom.:
Cov.:
32
AF XY:
AC XY:
15
AN XY:
727248
show subpopulations
African (AFR)
AF:
AC:
1
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
1
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
AC:
1
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
25
AN:
1112012
Other (OTH)
AF:
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.473
Heterozygous variant carriers
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3
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Allele balance
Age Distribution
Exome Het
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Age
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152218Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74368 show subpopulations
GnomAD4 genome
AF:
AC:
3
AN:
152218
Hom.:
Cov.:
33
AF XY:
AC XY:
2
AN XY:
74368
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41454
American (AMR)
AF:
AC:
0
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5200
South Asian (SAS)
AF:
AC:
0
AN:
4822
European-Finnish (FIN)
AF:
AC:
0
AN:
10618
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68048
Other (OTH)
AF:
AC:
2
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.558
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
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0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
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Age
Alfa
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Bravo
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Bethlem myopathy 1A Benign:1
Jul 01, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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