Variant 11-124123375-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001130142.2(VWA5A):c.940A>T(p.Ile314Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000192 in 1,613,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

VWA5A
NM_001130142.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.127

Variant links:

Genes affected

VWA5A (HGNC:6658): (von Willebrand factor A domain containing 5A) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

VWA5A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18728593).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
VWA5A	NM_001130142.2 linkuse as main transcript	c.940A>T	p.Ile314Phe	missense_variant	9/19	ENST00000456829.7	NP_001123614.1
VWA5A	NM_014622.5 linkuse as main transcript	c.940A>T	p.Ile314Phe	missense_variant	8/18		NP_055437.2
VWA5A	NM_198315.3 linkuse as main transcript	c.940A>T	p.Ile314Phe	missense_variant	8/10		NP_938057.1
VWA5A	XM_011542828.3 linkuse as main transcript	c.988A>T	p.Ile330Phe	missense_variant	9/19		XP_011541130.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWA5A	ENST00000456829.7 linkuse as main transcript	c.940A>T	p.Ile314Phe	missense_variant	9/19	1	NM_001130142.2	ENSP00000407726	P1	O00534-1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000638

AC:

AN:

250894

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135600

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000204

AC:

298

AN:

1461372

Hom.:

Cov.:

AF XY:

0.000206

AC XY:

150

AN XY:

726968

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000249

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152052

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000112

Hom.:

Bravo

AF:

0.0000945

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000296

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

Jan 03, 2024

The c.940A>T (p.I314F) alteration is located in exon 9 (coding exon 7) of the VWA5A gene. This alteration results from a A to T substitution at nucleotide position 940, causing the isoleucine (I) at amino acid position 314 to be replaced by a phenylalanine (F). 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

0.18

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.013

T;.;.;T;T

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.64

LIST_S2

Uncertain

0.96

.;.;D;D;D

M_CAP

Benign

0.0089

MetaRNN

Benign

0.19

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.0

M;M;M;M;.

MutationTaster

Benign

0.90

D;D;D;D;D;D;D;D

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.0

D;D;D;D;D

REVEL

Benign

0.13

Sift

Benign

0.12

T;T;T;T;T

Sift4G

Uncertain

0.023

D;T;T;D;T

Polyphen

0.57

P;.;.;P;B

Vest4

0.39

MVP

0.014

MPC

0.091

ClinPred

0.28

GERP RS

-0.88

Varity_R

0.10

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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