Variant X-154680220-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001081573.3(GAB3):c.1559G>C(p.Ser520Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00277 in 1,204,802 control chromosomes in the GnomAD database, including 119 homozygotes. There are 996 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0040 ( 20 hom., 125 hem., cov: 23)

Exomes 𝑓: 0.0026 ( 99 hom. 871 hem. )

Consequence

GAB3
NM_001081573.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.980

Variant links:

Genes affected

GAB3 (HGNC:17515): (GRB2 associated binding protein 3) This gene is a member of the GRB2-associated binding protein gene family. These proteins are scaffolding/docking proteins that are involved in several growth factor and cytokine signaling pathways, and they contain a pleckstrin homology domain, and bind SHP2 tyrosine phosphatase and GRB2 adapter protein. The protein encoded by this gene facilitates macrophage differentiation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

GAB3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021286607).

BP6

Variant X-154680220-C-G is Benign according to our data. Variant chrX-154680220-C-G is described in ClinVar as [Benign]. Clinvar id is 779994.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAB3	NM_001081573.3 linkuse as main transcript	c.1559G>C	p.Ser520Thr	missense_variant	9/10	ENST00000424127.3	NP_001075042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAB3	ENST00000424127.3 linkuse as main transcript	c.1559G>C	p.Ser520Thr	missense_variant	9/10	1	NM_001081573.3	ENSP00000399588	A2	Q8WWW8-2

Frequencies

GnomAD3 genomes

AF:

0.00406

AC:

452

AN:

111317

Hom.:

Cov.:

AF XY:

0.00373

AC XY:

125

AN XY:

33503

show subpopulations

Gnomad AFR

AF:

0.00163

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00258

Gnomad ASJ

AF:

0.00342

Gnomad EAS

AF:

0.0986

Gnomad SAS

AF:

0.00302

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000566

Gnomad OTH

AF:

0.00470

GnomAD3 exomes

AF:

0.00856

AC:

1545

AN:

180493

Hom.:

AF XY:

0.00709

AC XY:

461

AN XY:

65051

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00351

Gnomad EAS exome

AF:

0.108

Gnomad SAS exome

AF:

0.00129

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000495

Gnomad OTH exome

AF:

0.00610

GnomAD4 exome

AF:

0.00264

AC:

2892

AN:

1093430

Hom.:

Cov.:

AF XY:

0.00243

AC XY:

871

AN XY:

358936

show subpopulations

Gnomad4 AFR exome

AF:

0.00103

Gnomad4 AMR exome

AF:

0.0000571

Gnomad4 ASJ exome

AF:

0.00316

Gnomad4 EAS exome

AF:

0.0793

Gnomad4 SAS exome

AF:

0.00121

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000429

Gnomad4 OTH exome

AF:

0.00686

GnomAD4 genome

AF:

0.00405

AC:

451

AN:

111372

Hom.:

Cov.:

AF XY:

0.00372

AC XY:

125

AN XY:

33568

show subpopulations

Gnomad4 AFR

AF:

0.00163

Gnomad4 AMR

AF:

0.00257

Gnomad4 ASJ

AF:

0.00342

Gnomad4 EAS

AF:

0.0983

Gnomad4 SAS

AF:

0.00303

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000566

Gnomad4 OTH

AF:

0.00531

Alfa

AF:

0.00300

Hom.:

Bravo

AF:

0.00432

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000692

AC:

ESP6500AA

AF:

0.00156

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.00745

AC:

904

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 17, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.89

CADD

Benign

9.8

DANN

Benign

0.50

DEOGEN2

Benign

0.14

T;.

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.58

T;T

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.98

N;N

REVEL

Benign

0.025

Sift

Benign

0.47

T;T

Sift4G

Benign

0.39

T;T

Polyphen

0.094

B;.

Vest4

0.058

MVP

0.26

MPC

0.31

ClinPred

0.0089

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.18

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