Variant chr1-107609935-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006113.5(VAV3):c.2011C>A(p.Pro671Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00254 in 1,613,210 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 5 hom. )

Consequence

VAV3
NM_006113.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.89

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0124848485).

BP6

Variant 1-107609935-G-T is Benign according to our data. Variant chr1-107609935-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 773149.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 286 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VAV3	NM_006113.5 linkuse as main transcript	c.2011C>A	p.Pro671Thr	missense_variant	22/27	ENST00000370056.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VAV3	ENST00000370056.9 linkuse as main transcript	c.2011C>A	p.Pro671Thr	missense_variant	22/27	1	NM_006113.5	P1	Q9UKW4-1

Frequencies

GnomAD3 genomes

AF:

0.00188

AC:

286

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000917

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00360

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00276

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00178

AC:

448

AN:

251084

Hom.:

AF XY:

0.00167

AC XY:

227

AN XY:

135696

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.00336

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00258

Gnomad OTH exome

AF:

0.00344

GnomAD4 exome

AF:

0.00260

AC:

3805

AN:

1460924

Hom.:

Cov.:

AF XY:

0.00246

AC XY:

1786

AN XY:

726762

show subpopulations

Gnomad4 AFR exome

AF:

0.000658

Gnomad4 AMR exome

AF:

0.00340

Gnomad4 ASJ exome

AF:

0.0000767

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000325

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.00304

Gnomad4 OTH exome

AF:

0.00305

GnomAD4 genome

AF:

0.00188

AC:

286

AN:

152286

Hom.:

Cov.:

AF XY:

0.00164

AC XY:

122

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000914

Gnomad4 AMR

AF:

0.00360

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00276

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00261

Hom.:

Bravo

AF:

0.00222

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00209

AC:

ExAC

AF:

0.00157

AC:

191

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00432

EpiControl

AF:

0.00309

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Aug 01, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.18

T;.;.

Eigen

Benign

-0.12

Eigen_PC

Benign

0.073

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.68

T;T;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.012

T;T;T

MetaSVM

Benign

-0.33

MutationAssessor

Benign

1.5

L;L;.

MutationTaster

Benign

0.91

D;D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-2.3

N;N;D

REVEL

Benign

0.13

Sift

Benign

0.57

T;T;T

Sift4G

Benign

0.26

T;T;T

Polyphen

0.0

B;.;B

Vest4

0.45

MVP

0.84

MPC

0.21

ClinPred

0.029

GERP RS

5.1

Varity_R

0.23

gMVP

0.43

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