Variant 16-22110952-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_173615.5(VWA3A):c.647C>T(p.Ala216Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000462 in 1,610,336 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00045 ( 4 hom. )

Consequence

VWA3A
NM_173615.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.444

Variant links:

Genes affected

VWA3A (HGNC:27088): (von Willebrand factor A domain containing 3A) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

VWA3A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007252872).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWA3A	NM_173615.5 linkuse as main transcript	c.647C>T	p.Ala216Val	missense_variant	8/34	ENST00000389398.10	NP_775886.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWA3A	ENST00000389398.10 linkuse as main transcript	c.647C>T	p.Ala216Val	missense_variant	8/34	5	NM_173615.5	ENSP00000374049	P1	A6NCI4-1

Frequencies

GnomAD3 genomes

AF:

0.000558

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000676

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000738

AC:

179

AN:

242602

Hom.:

AF XY:

0.000739

AC XY:

AN XY:

131262

show subpopulations

Gnomad AFR exome

AF:

0.0000670

Gnomad AMR exome

AF:

0.000650

Gnomad ASJ exome

AF:

0.00423

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000239

Gnomad FIN exome

AF:

0.0000473

Gnomad NFE exome

AF:

0.000900

Gnomad OTH exome

AF:

0.00119

GnomAD4 exome

AF:

0.000452

AC:

659

AN:

1457998

Hom.:

Cov.:

AF XY:

0.000446

AC XY:

323

AN XY:

724772

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000859

Gnomad4 ASJ exome

AF:

0.00392

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000223

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000385

Gnomad4 OTH exome

AF:

0.000863

GnomAD4 genome

AF:

0.000558

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.000537

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000676

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000898

Hom.:

Bravo

AF:

0.000778

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000710

AC:

ExAC

AF:

0.000727

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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 21, 2022

The c.647C>T (p.A216V) alteration is located in exon 8 (coding exon 8) of the VWA3A gene. This alteration results from a C to T substitution at nucleotide position 647, causing the alanine (A) at amino acid position 216 to be replaced by a valine (V). 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

0.081

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.56

CADD

Benign

1.7

DANN

Benign

0.41

DEOGEN2

Benign

0.00080

.;.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.60

.;.;T

M_CAP

Benign

0.0041

MetaRNN

Benign

0.0073

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.13

.;.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.050

Sift

Benign

0.066

T;T;T

Sift4G

Benign

0.10

T;T;T

Polyphen

0.0010

.;.;B

Vest4

0.095

MVP

0.014

MPC

0.044

ClinPred

0.0069

GERP RS

2.1

Varity_R

0.018

gMVP

0.11

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