Variant 3-130379531-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001278298.2(COL6A5):c.781A>C(p.Ile261Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

COL6A5
NM_001278298.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.180

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]

COL6A5 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.061939).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
COL6A5	NM_001278298.2 linkuse as main transcript	c.781A>C	p.Ile261Leu	missense_variant	4/41	ENST00000373157.9	NP_001265227.1
COL6A5	NM_153264.7 linkuse as main transcript	c.781A>C	p.Ile261Leu	missense_variant	4/40		NP_694996.5
COL6A5	NR_022012.3 linkuse as main transcript	n.1119A>C		non_coding_transcript_exon_variant	4/42

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL6A5	ENST00000373157.9 linkuse as main transcript	c.781A>C	p.Ile261Leu	missense_variant	4/41	2	NM_001278298.2	ENSP00000362250	P2
COL6A5	ENST00000312481.11 linkuse as main transcript	c.781A>C	p.Ile261Leu	missense_variant, NMD_transcript_variant	4/42	1		ENSP00000309762		A8TX70-1
COL6A5	ENST00000512836.6 linkuse as main transcript	c.781A>C	p.Ile261Leu	missense_variant	4/40	2		ENSP00000422898	A2	A8TX70-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.15e-7

AC:

AN:

1399176

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

690106

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 30, 2022

The c.781A>C (p.I261L) alteration is located in exon 4 (coding exon 3) of the COL6A5 gene. This alteration results from a A to C substitution at nucleotide position 781, causing the isoleucine (I) at amino acid position 261 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

0.98

DANN

Benign

0.85

DEOGEN2

Benign

0.059

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.53

M_CAP

Benign

0.011

MetaRNN

Benign

0.062

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.1

REVEL

Benign

0.097

Sift

Benign

0.30

Sift4G

Benign

0.087

Vest4

0.14

MutPred

0.52

Gain of disorder (P = 0.0769);

MVP

0.14

MPC

0.036

ClinPred

0.037

GERP RS

1.4

gMVP

0.36

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over