Variant 16-22100469-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_173615.5(VWA3A):c.404G>A(p.Arg135His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000529 in 1,551,384 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000054 ( 0 hom. )

Consequence

VWA3A
NM_173615.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.552

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:

VWA3A (HGNC:):

VWA3A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0065046847).

BP6

Variant 16-22100469-G-A is Benign according to our data. Variant chr16-22100469-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3189241.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWA3A	NM_173615.5 linkuse as main transcript	c.404G>A	p.Arg135His	missense_variant	5/34	ENST00000389398.10	NP_775886.3	A6NCI4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWA3A	ENST00000389398.10 linkuse as main transcript	c.404G>A	p.Arg135His	missense_variant	5/34	5	NM_173615.5	ENSP00000374049.5		A6NCI4-1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

151984

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000153

AC:

AN:

156462

Hom.:

AF XY:

0.0000965

AC XY:

AN XY:

82936

show subpopulations

Gnomad AFR exome

AF:

0.000126

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00130

Gnomad EAS exome

AF:

0.000275

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.000228

GnomAD4 exome

AF:

0.0000543

AC:

AN:

1399400

Hom.:

Cov.:

AF XY:

0.0000637

AC XY:

AN XY:

690212

show subpopulations

Gnomad4 AFR exome

AF:

0.0000316

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.00111

Gnomad4 EAS exome

AF:

0.000140

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000278

Gnomad4 OTH exome

AF:

0.000155

GnomAD4 genome

AF:

0.0000395

AC:

AN:

151984

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74232

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000360

Hom.:

Bravo

AF:

0.0000793

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.000314

AC:

ExAC

AF:

0.000243

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.39

DANN

Benign

0.36

DEOGEN2

Benign

0.00031

.;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.55

.;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.0065

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-2.1

.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.18

PROVEAN

Benign

-0.17

N;N

REVEL

Benign

0.025

Sift

Benign

0.66

T;T

Sift4G

Benign

0.50

T;T

Polyphen

0.0

.;B

Vest4

0.060

MVP

0.014

MPC

0.050

ClinPred

0.018

GERP RS

-4.1

Varity_R

0.023

gMVP

0.063

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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