Variant 1-107964797-A-G 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.73T>C(p.Trp25Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00194 in 1,613,956 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 6 hom. )

Consequence

VAV3
NM_006113.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.12

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-AS1 (HGNC:40608): (VAV3 antisense RNA 1)

VAV3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00974074).

BP6

Variant 1-107964797-A-G is Benign according to our data. Variant chr1-107964797-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 709763.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 200 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAV3	NM_006113.5 linkuse as main transcript	c.73T>C	p.Trp25Arg	missense_variant	1/27	ENST00000370056.9	NP_006104.4
VAV3-AS1	NR_046653.1 linkuse as main transcript	n.62+293A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAV3	ENST00000370056.9 linkuse as main transcript	c.73T>C	p.Trp25Arg	missense_variant	1/27	1	NM_006113.5	ENSP00000359073	P1	Q9UKW4-1
VAV3	ENST00000527011.5 linkuse as main transcript	c.73T>C	p.Trp25Arg	missense_variant	1/28	1		ENSP00000432540		Q9UKW4-4
VAV3-AS1	ENST00000438318.1 linkuse as main transcript	n.62+293A>G		intron_variant, non_coding_transcript_variant		2
VAV3	ENST00000490388.2 linkuse as main transcript	c.58T>C	p.Trp20Arg	missense_variant	1/20	2		ENSP00000433559

Frequencies

GnomAD3 genomes

AF:

0.00131

AC:

200

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000660

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00219

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00121

AC:

304

AN:

250582

Hom.:

AF XY:

0.00111

AC XY:

151

AN XY:

135698

show subpopulations

Gnomad AFR exome

AF:

0.000433

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00143

Gnomad NFE exome

AF:

0.00227

Gnomad OTH exome

AF:

0.000818

GnomAD4 exome

AF:

0.00200

AC:

2925

AN:

1461698

Hom.:

Cov.:

AF XY:

0.00187

AC XY:

1361

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00128

Gnomad4 NFE exome

AF:

0.00249

Gnomad4 OTH exome

AF:

0.00131

GnomAD4 genome

AF:

0.00131

AC:

200

AN:

152258

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000660

Gnomad4 NFE

AF:

0.00219

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00210

Hom.:

Bravo

AF:

0.00138

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00221

AC:

ExAC

AF:

0.00133

AC:

162

EpiCase

AF:

0.00158

EpiControl

AF:

0.000830

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

Labcorp Genetics (formerly Invitae), Labcorp

Jul 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.71

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Benign

0.40

T;.

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.066

MetaRNN

Benign

0.0097

T;T

MetaSVM

Benign

-0.69

MutationAssessor

Benign

1.9

L;L

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-4.7

D;D

REVEL

Benign

0.18

Sift

Benign

0.065

T;T

Sift4G

Uncertain

0.0040

D;D

Polyphen

0.27

B;.

Vest4

0.43

MutPred

0.61

Gain of disorder (P = 0.0121);Gain of disorder (P = 0.0121);

MVP

0.71

MPC

0.77

ClinPred

0.043

GERP RS

5.0

Varity_R

0.64

gMVP

0.83

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