chr3-130376262-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001278298.2(COL6A5):​c.93C>T​(p.Val31Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000631 in 1,607,912 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00038 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00066 ( 0 hom. )

Consequence

COL6A5
NM_001278298.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.27
Variant links:
Genes affected
COL6A5 (HGNC:26674): (collagen type VI alpha 5 chain) This gene encodes a member of the collagen superfamily of proteins. The encoded protein contains multiple von Willebrand factor A-like domains and may interact with the alpha 1 and alpha 2 chains of collagen VI to form the complete collagen VI trimer. Polymorphisms in this gene may be linked to dermal phenotypes, such as eczema. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
Variant 3-130376262-C-T is Benign according to our data. Variant chr3-130376262-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3388395.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-4.27 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COL6A5NM_001278298.2 linkc.93C>T p.Val31Val synonymous_variant 3/41 ENST00000373157.9 NP_001265227.1 A8TX70H0Y393
COL6A5NM_153264.7 linkc.93C>T p.Val31Val synonymous_variant 3/40 NP_694996.5 A8TX70-2
COL6A5NR_022012.3 linkn.431C>T non_coding_transcript_exon_variant 3/42

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
COL6A5ENST00000373157.9 linkc.93C>T p.Val31Val synonymous_variant 3/412 NM_001278298.2 ENSP00000362250.5 H0Y393
COL6A5ENST00000312481.11 linkn.93C>T non_coding_transcript_exon_variant 3/421 ENSP00000309762.7 A8TX70-1
COL6A5ENST00000512836.6 linkc.93C>T p.Val31Val synonymous_variant 3/402 ENSP00000422898.2 A8TX70-2H0Y935

Frequencies

GnomAD3 genomes
AF:
0.000381
AC:
58
AN:
152132
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000706
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000461
AC:
112
AN:
242870
Hom.:
0
AF XY:
0.000409
AC XY:
54
AN XY:
131944
show subpopulations
Gnomad AFR exome
AF:
0.000325
Gnomad AMR exome
AF:
0.0000890
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000382
Gnomad NFE exome
AF:
0.000837
Gnomad OTH exome
AF:
0.000685
GnomAD4 exome
AF:
0.000657
AC:
956
AN:
1455780
Hom.:
0
Cov.:
32
AF XY:
0.000637
AC XY:
461
AN XY:
724032
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000681
Gnomad4 ASJ exome
AF:
0.0000781
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000339
Gnomad4 NFE exome
AF:
0.000812
Gnomad4 OTH exome
AF:
0.000549
GnomAD4 genome
AF:
0.000381
AC:
58
AN:
152132
Hom.:
1
Cov.:
32
AF XY:
0.000404
AC XY:
30
AN XY:
74288
show subpopulations
Gnomad4 AFR
AF:
0.000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000706
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000751
Hom.:
0
Bravo
AF:
0.000393

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenNov 01, 2024COL6A5: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.70
CADD
Benign
1.9
DANN
Benign
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs375962998; hg19: chr3-130095105; COSMIC: COSV55203570; API