3-130379780-C-G

Position:

chr3-130379780-C-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001278298.2(COL6A5):c.1030C>G(p.Leu344Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00264 in 1,551,416 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 10 hom. )

Consequence

COL6A5
NM_001278298.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.0690

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009050518).

BP6

Variant 3-130379780-C-G is Benign according to our data. Variant chr3-130379780-C-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2337907.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
COL6A5	NM_001278298.2 linkuse as main transcript	c.1030C>G	p.Leu344Val	missense_variant	4/41	ENST00000373157.9	NP_001265227.1
COL6A5	NM_153264.7 linkuse as main transcript	c.1030C>G	p.Leu344Val	missense_variant	4/40		NP_694996.5
COL6A5	NR_022012.3 linkuse as main transcript	n.1368C>G		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.1030C>G	p.Leu344Val	missense_variant	4/41	2	NM_001278298.2	ENSP00000362250	P2
COL6A5	ENST00000312481.11 linkuse as main transcript	c.1030C>G	p.Leu344Val	missense_variant, NMD_transcript_variant	4/42	1		ENSP00000309762		A8TX70-1
COL6A5	ENST00000512836.6 linkuse as main transcript	c.1030C>G	p.Leu344Val	missense_variant	4/40	2		ENSP00000422898	A2	A8TX70-2

Frequencies

GnomAD3 genomes

AF:

0.00201

AC:

305

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.000866

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00169

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00363

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00151

AC:

231

AN:

153436

Hom.:

AF XY:

0.00145

AC XY:

118

AN XY:

81380

show subpopulations

Gnomad AFR exome

AF:

0.000379

Gnomad AMR exome

AF:

0.000527

Gnomad ASJ exome

AF:

0.000590

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00157

Gnomad NFE exome

AF:

0.00306

Gnomad OTH exome

AF:

0.00116

GnomAD4 exome

AF:

0.00271

AC:

3785

AN:

1399204

Hom.:

Cov.:

AF XY:

0.00269

AC XY:

1856

AN XY:

690110

show subpopulations

Gnomad4 AFR exome

AF:

0.000285

Gnomad4 AMR exome

AF:

0.000364

Gnomad4 ASJ exome

AF:

0.000755

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00227

Gnomad4 NFE exome

AF:

0.00325

Gnomad4 OTH exome

AF:

0.00219

GnomAD4 genome

AF:

0.00200

AC:

305

AN:

152212

Hom.:

Cov.:

AF XY:

0.00168

AC XY:

125

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.000866

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00169

Gnomad4 NFE

AF:

0.00363

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00278

Hom.:

Bravo

AF:

0.00183

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00104

AC:

ExAC

AF:

0.000968

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2021

The c.1030C>G (p.L344V) alteration is located in exon 4 (coding exon 3) of the COL6A5 gene. This alteration results from a C to G substitution at nucleotide position 1030, causing the leucine (L) at amino acid position 344 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

COL6A5: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.78

M_CAP

Benign

0.014

MetaRNN

Benign

0.0091

MetaSVM

Benign

-0.81

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.9

REVEL

Benign

0.27

Sift

Benign

0.34

Sift4G

Pathogenic

0.0010

Vest4

0.13

MVP

0.40

MPC

0.11

ClinPred

0.031

GERP RS

3.4

gMVP

0.35

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