Variant chr11-124124271-C-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.1199C>T(p.Thr400Met) variant causes a missense change. The variant allele was found at a frequency of 0.000253 in 1,613,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

VWA5A
NM_001130142.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.68

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=0.16299462).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWA5A	NM_001130142.2 linkuse as main transcript	c.1199C>T	p.Thr400Met	missense_variant	11/19	ENST00000456829.7	NP_001123614.1	O00534-1A0A024R3H3
VWA5A	NM_014622.5 linkuse as main transcript	c.1199C>T	p.Thr400Met	missense_variant	10/18		NP_055437.2	O00534-1A0A024R3H3
VWA5A	NM_198315.3 linkuse as main transcript	c.1199C>T	p.Thr400Met	missense_variant	10/10		NP_938057.1	O00534-3
VWA5A	XM_011542828.3 linkuse as main transcript	c.1247C>T	p.Thr416Met	missense_variant	11/19		XP_011541130.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWA5A	ENST00000456829.7 linkuse as main transcript	c.1199C>T	p.Thr400Met	missense_variant	11/19	1	NM_001130142.2	ENSP00000407726.2		O00534-1

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000397

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000131

AC:

AN:

251152

Hom.:

AF XY:

0.000147

AC XY:

AN XY:

135756

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:

0.0000655

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000258

AC:

377

AN:

1461660

Hom.:

Cov.:

AF XY:

0.000259

AC XY:

188

AN XY:

727118

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:

0.0000812

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000320

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000204

AC:

AN:

152132

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000211

Hom.:

Bravo

AF:

0.000196

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000189

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000178

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

Aug 01, 2022

The c.1199C>T (p.T400M) alteration is located in exon 11 (coding exon 9) of the VWA5A gene. This alteration results from a C to T substitution at nucleotide position 1199, causing the threonine (T) at amino acid position 400 to be replaced by a methionine (M). 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

0.17

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.34

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.061

T;.;.;T;T

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.86

.;.;D;D;D

M_CAP

Benign

0.044

MetaRNN

Benign

0.16

T;T;T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Pathogenic

3.0

M;M;M;M;.

MutationTaster

Benign

1.0

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

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-5.6

D;D;D;D;D

REVEL

Benign

0.25

Sift

Pathogenic

0.0

D;T;T;D;T

Sift4G

Pathogenic

0.0010

D;D;D;D;D

Polyphen

1.0

D;.;.;D;D

Vest4

0.53

MVP

0.081

MPC

0.26

ClinPred

0.88

GERP RS

4.4

Varity_R

0.70

gMVP

0.41

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