Variant 13-41615006-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM5BP4_StrongBP6_ModerateBS2

The NM_015058.2(VWA8):c.4690G>A(p.Val1564Met) variant causes a missense change. The variant allele was found at a frequency of 0.00662 in 1,613,696 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1564L) has been classified as Likely pathogenic.

Frequency

Genomes: 𝑓 0.0046 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0068 ( 38 hom. )

Consequence

VWA8
NM_015058.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.86

Variant links:

Genes affected

VWA8 (HGNC:29071): (von Willebrand factor A domain containing 8) Predicted to enable ATP binding activity. Located in mitochondrion and peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

VWA8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM5

Other missense variant is known to change same aminoacid residue: Variant chr13-41615006-C-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 617837.Status of the report is no_assertion_criteria_provided, 0 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.010855824).

BP6

Variant 13-41615006-C-T is Benign according to our data. Variant chr13-41615006-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2672545.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 695 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VWA8	NM_015058.2 linkuse as main transcript	c.4690G>A	p.Val1564Met	missense_variant	38/45	ENST00000379310.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VWA8	ENST00000379310.8 linkuse as main transcript	c.4690G>A	p.Val1564Met	missense_variant	38/45	2	NM_015058.2	P1	A3KMH1-1

Frequencies

GnomAD3 genomes

AF:

0.00457

AC:

695

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00147

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00332

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00766

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00456

AC:

1137

AN:

249350

Hom.:

AF XY:

0.00465

AC XY:

629

AN XY:

135286

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00333

Gnomad ASJ exome

AF:

0.00258

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00232

Gnomad FIN exome

AF:

0.00186

Gnomad NFE exome

AF:

0.00749

Gnomad OTH exome

AF:

0.00314

GnomAD4 exome

AF:

0.00684

AC:

9993

AN:

1461420

Hom.:

Cov.:

AF XY:

0.00666

AC XY:

4839

AN XY:

727038

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.00309

Gnomad4 ASJ exome

AF:

0.00142

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00269

Gnomad4 FIN exome

AF:

0.00197

Gnomad4 NFE exome

AF:

0.00822

Gnomad4 OTH exome

AF:

0.00489

GnomAD4 genome

AF:

0.00456

AC:

694

AN:

152276

Hom.:

Cov.:

AF XY:

0.00445

AC XY:

331

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00147

Gnomad4 AMR

AF:

0.00419

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.00764

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.00582

Hom.:

Bravo

AF:

0.00431

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.00124

AC:

ESP6500EA

AF:

0.00990

AC:

ExAC

AF:

0.00453

AC:

548

EpiCase

AF:

0.00682

EpiControl

AF:

0.00736

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 submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2023

VWA8: PM5, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.26

Cadd

Benign

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.12

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.0058

MetaRNN

Benign

0.011

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-2.3

REVEL

Benign

0.15

Sift

Uncertain

0.015

Sift4G

Uncertain

0.023

Polyphen

1.0

Vest4

0.69

MVP

0.19

MPC

0.36

ClinPred

0.023

GERP RS

6.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.66

Splicing

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