Variant 3-130379810-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001278298.2(COL6A5):c.1060G>T(p.Val354Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000757 in 1,551,394 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00052 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00078 ( 2 hom. )

Consequence

COL6A5
NM_001278298.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.91

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007045418).

BP6

Variant 3-130379810-G-T is Benign according to our data. Variant chr3-130379810-G-T is described in ClinVar as [Benign]. Clinvar id is 3239010.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
COL6A5	NM_001278298.2 linkuse as main transcript	c.1060G>T	p.Val354Leu	missense_variant	4/41	ENST00000373157.9	NP_001265227.1
COL6A5	NM_153264.7 linkuse as main transcript	c.1060G>T	p.Val354Leu	missense_variant	4/40		NP_694996.5
COL6A5	NR_022012.3 linkuse as main transcript	n.1398G>T		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.1060G>T	p.Val354Leu	missense_variant	4/41	2	NM_001278298.2	ENSP00000362250	P2
COL6A5	ENST00000312481.11 linkuse as main transcript	c.1060G>T	p.Val354Leu	missense_variant, NMD_transcript_variant	4/42	1		ENSP00000309762		A8TX70-1
COL6A5	ENST00000512836.6 linkuse as main transcript	c.1060G>T	p.Val354Leu	missense_variant	4/40	2		ENSP00000422898	A2	A8TX70-2

Frequencies

GnomAD3 genomes

AF:

0.000519

AC:

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

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:

0.00103

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000508

AC:

AN:

153582

Hom.:

AF XY:

0.000540

AC XY:

AN XY:

81468

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000918

Gnomad SAS exome

AF:

0.000439

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000996

Gnomad OTH exome

AF:

0.000695

GnomAD4 exome

AF:

0.000783

AC:

1095

AN:

1399194

Hom.:

Cov.:

AF XY:

0.000742

AC XY:

512

AN XY:

690108

show subpopulations

Gnomad4 AFR exome

AF:

0.0000950

Gnomad4 AMR exome

AF:

0.000280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.000480

Gnomad4 FIN exome

AF:

0.0000203

Gnomad4 NFE exome

AF:

0.000909

Gnomad4 OTH exome

AF:

0.000914

GnomAD4 genome

AF:

0.000519

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.000511

AC XY:

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00103

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000919

Hom.:

Bravo

AF:

0.000457

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000483

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2024

COL6A5: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

Eigen

Benign

0.11

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.76

M_CAP

Benign

0.025

MetaRNN

Benign

0.0070

MetaSVM

Benign

-0.41

MutationTaster

Benign

0.80

N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-2.3

REVEL

Uncertain

0.42

Sift

Benign

0.083

Sift4G

Benign

0.14

Vest4

0.27

MutPred

0.57

Gain of disorder (P = 0.1596);

MVP

0.46

MPC

0.18

ClinPred

0.072

GERP RS

4.5

gMVP

0.51

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over