Variant 13-41692935-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_015058.2(VWA8):c.3602C>T(p.Ala1201Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000636 in 1,611,100 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00034 ( 3 hom. )

Consequence

VWA8
NM_015058.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.05

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:

VWA8 (HGNC:):

VWA8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010804683).

BP6

Variant 13-41692935-G-A is Benign according to our data. Variant chr13-41692935-G-A is described in ClinVar as [Benign]. Clinvar id is 708894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 528 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWA8	NM_015058.2 linkuse as main transcript	c.3602C>T	p.Ala1201Val	missense_variant	30/45	ENST00000379310.8	NP_055873.1	A3KMH1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWA8	ENST00000379310.8 linkuse as main transcript	c.3602C>T	p.Ala1201Val	missense_variant	30/45	2	NM_015058.2	ENSP00000368612.3		A3KMH1-1
VWA8	ENST00000478987.1 linkuse as main transcript	n.89C>T		non_coding_transcript_exon_variant	2/6	4

Frequencies

GnomAD3 genomes

AF:

0.00344

AC:

522

AN:

151652

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0114

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00250

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:

0.0000884

Gnomad OTH

AF:

0.00288

GnomAD3 exomes

AF:

0.000833

AC:

207

AN:

248434

Hom.:

AF XY:

0.000608

AC XY:

AN XY:

134816

show subpopulations

Gnomad AFR exome

AF:

0.0110

Gnomad AMR exome

AF:

0.000963

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000655

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000341

AC:

497

AN:

1459340

Hom.:

Cov.:

AF XY:

0.000280

AC XY:

203

AN XY:

725960

show subpopulations

Gnomad4 AFR exome

AF:

0.0108

Gnomad4 AMR exome

AF:

0.000987

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000216

Gnomad4 OTH exome

AF:

0.000979

GnomAD4 genome

AF:

0.00348

AC:

528

AN:

151760

Hom.:

Cov.:

AF XY:

0.00340

AC XY:

252

AN XY:

74144

show subpopulations

Gnomad4 AFR

AF:

0.0115

Gnomad4 AMR

AF:

0.00250

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000884

Gnomad4 OTH

AF:

0.00286

Alfa

AF:

0.000586

Hom.:

Bravo

AF:

0.00391

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0131

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00107

AC:

129

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.57

DEOGEN2

Benign

0.016

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.44

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.68

MetaRNN

Benign

0.011

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.87

REVEL

Benign

0.054

Sift

Benign

0.41

Sift4G

Benign

0.50

Polyphen

0.30

Vest4

0.26

MVP

0.014

MPC

0.057

ClinPred

0.016

GERP RS

2.8

Varity_R

0.040

gMVP

0.48

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