Variant rs7528153 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006113.5(VAV3):c.892A>T(p.Thr298Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 1,611,246 control chromosomes in the GnomAD database, including 355,014 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.63 ( 31093 hom., cov: 32)

Exomes 𝑓: 0.66 ( 323921 hom. )

Consequence

VAV3
NM_006113.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.851

Variant links:

Genes affected

VAV3 (HGNC:12659): (vav guanine nucleotide exchange factor 3) This gene is a member of the VAV gene family. The VAV proteins are guanine nucleotide exchange factors (GEFs) for Rho family GTPases that activate pathways leading to actin cytoskeletal rearrangements and transcriptional alterations. This gene product acts as a GEF preferentially for RhoG, RhoA, and to a lesser extent, RAC1, and it associates maximally with the nucleotide-free states of these GTPases. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

VAV3 links:

VAV3 (HGNC:):

VAV3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.0051121E-6).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAV3	NM_006113.5 linkuse as main transcript	c.892A>T	p.Thr298Ser	missense_variant	9/27	ENST00000370056.9	NP_006104.4	Q9UKW4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAV3	ENST00000370056.9 linkuse as main transcript	c.892A>T	p.Thr298Ser	missense_variant	9/27	1	NM_006113.5	ENSP00000359073.4		Q9UKW4-1

Frequencies

GnomAD3 genomes

AF:

0.633

AC:

96056

AN:

151864

Hom.:

31083

Cov.:

show subpopulations

Gnomad AFR

AF:

0.605

Gnomad AMI

AF:

0.488

Gnomad AMR

AF:

0.532

Gnomad ASJ

AF:

0.662

Gnomad EAS

AF:

0.395

Gnomad SAS

AF:

0.385

Gnomad FIN

AF:

0.678

Gnomad MID

AF:

0.661

Gnomad NFE

AF:

0.701

Gnomad OTH

AF:

0.637

GnomAD3 exomes

AF:

0.584

AC:

146399

AN:

250758

Hom.:

45528

AF XY:

0.586

AC XY:

79511

AN XY:

135586

show subpopulations

Gnomad AFR exome

AF:

0.603

Gnomad AMR exome

AF:

0.386

Gnomad ASJ exome

AF:

0.658

Gnomad EAS exome

AF:

0.388

Gnomad SAS exome

AF:

0.403

Gnomad FIN exome

AF:

0.685

Gnomad NFE exome

AF:

0.694

Gnomad OTH exome

AF:

0.619

GnomAD4 exome

AF:

0.658

AC:

960257

AN:

1459264

Hom.:

323921

Cov.:

AF XY:

0.652

AC XY:

473227

AN XY:

726038

show subpopulations

Gnomad4 AFR exome

AF:

0.602

Gnomad4 AMR exome

AF:

0.402

Gnomad4 ASJ exome

AF:

0.657

Gnomad4 EAS exome

AF:

0.372

Gnomad4 SAS exome

AF:

0.407

Gnomad4 FIN exome

AF:

0.685

Gnomad4 NFE exome

AF:

0.699

Gnomad4 OTH exome

AF:

0.646

GnomAD4 genome

AF:

0.632

AC:

96106

AN:

151982

Hom.:

31093

Cov.:

AF XY:

0.626

AC XY:

46506

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.605

Gnomad4 AMR

AF:

0.531

Gnomad4 ASJ

AF:

0.662

Gnomad4 EAS

AF:

0.396

Gnomad4 SAS

AF:

0.384

Gnomad4 FIN

AF:

0.678

Gnomad4 NFE

AF:

0.701

Gnomad4 OTH

AF:

0.634

Alfa

AF:

0.675

Hom.:

26404

Bravo

AF:

0.618

TwinsUK

AF:

0.688

AC:

2552

ALSPAC

AF:

0.704

AC:

2713

ESP6500AA

AF:

0.613

AC:

2699

ESP6500EA

AF:

0.696

AC:

5984

ExAC

AF:

0.588

AC:

71363

Asia WGS

AF:

0.408

AC:

1420

AN:

3478

EpiCase

AF:

0.691

EpiControl

AF:

0.689

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.057

T;.

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.073

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.56

T;T

MetaRNN

Benign

0.0000030

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;L

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.16

N;N

REVEL

Benign

0.049

Sift

Benign

0.62

T;T

Sift4G

Benign

0.67

T;T

Polyphen

0.022

B;.

Vest4

0.074

MPC

0.17

ClinPred

0.027

GERP RS

4.5

Varity_R

0.051

gMVP

0.11

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over