chr2-135135802-A-G

Position:

chr2-135135802-A-G

Variant summary

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

The NM_012233.3(RAB3GAP1):c.1793A>G(p.Asn598Ser) variant causes a missense change. The variant allele was found at a frequency of 0.147 in 1,613,824 control chromosomes in the GnomAD database, including 24,629 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 2387 hom., cov: 32)

Exomes 𝑓: 0.15 ( 22242 hom. )

Consequence

RAB3GAP1
NM_012233.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 5.03

Variant links:

Genes affected

RAB3GAP1 (HGNC:17063): (RAB3 GTPase activating protein catalytic subunit 1) This gene encodes the catalytic subunit of a Rab GTPase activating protein. The encoded protein forms a heterodimer with a non-catalytic subunit to specifically regulate the activity of members of the Rab3 subfamily of small G proteins. This protein mediates the hydrolysis of GTP bound Rab3 to the GDP bound form. Mutations in this gene are associated with Warburg micro syndrome. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Feb 2010]

RAB3GAP1 links:

RAB3GAP1 (HGNC:):

RAB3GAP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003854096).

BP6

Variant 2-135135802-A-G is Benign according to our data. Variant chr2-135135802-A-G is described in ClinVar as [Benign]. Clinvar id is 130064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-135135802-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB3GAP1	NM_012233.3 linkuse as main transcript	c.1793A>G	p.Asn598Ser	missense_variant	17/24	ENST00000264158.13	NP_036365.1	Q15042-1B9A6J2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB3GAP1	ENST00000264158.13 linkuse as main transcript	c.1793A>G	p.Asn598Ser	missense_variant	17/24	1	NM_012233.3	ENSP00000264158.8		Q15042-1

Frequencies

GnomAD3 genomes

AF:

0.145

AC:

22013

AN:

152076

Hom.:

2384

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0371

Gnomad AMI

AF:

0.143

Gnomad AMR

AF:

0.229

Gnomad ASJ

AF:

0.400

Gnomad EAS

AF:

0.382

Gnomad SAS

AF:

0.294

Gnomad FIN

AF:

0.144

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.147

Gnomad OTH

AF:

0.204

GnomAD3 exomes

AF:

0.204

AC:

51342

AN:

251228

Hom.:

6992

AF XY:

0.211

AC XY:

28587

AN XY:

135778

show subpopulations

Gnomad AFR exome

AF:

0.0327

Gnomad AMR exome

AF:

0.249

Gnomad ASJ exome

AF:

0.397

Gnomad EAS exome

AF:

0.389

Gnomad SAS exome

AF:

0.295

Gnomad FIN exome

AF:

0.144

Gnomad NFE exome

AF:

0.154

Gnomad OTH exome

AF:

0.237

GnomAD4 exome

AF:

0.147

AC:

214878

AN:

1461630

Hom.:

22242

Cov.:

AF XY:

0.154

AC XY:

112059

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.0359

Gnomad4 AMR exome

AF:

0.244

Gnomad4 ASJ exome

AF:

0.392

Gnomad4 EAS exome

AF:

0.404

Gnomad4 SAS exome

AF:

0.287

Gnomad4 FIN exome

AF:

0.148

Gnomad4 NFE exome

AF:

0.118

Gnomad4 OTH exome

AF:

0.183

GnomAD4 genome

AF:

0.145

AC:

22033

AN:

152194

Hom.:

2387

Cov.:

AF XY:

0.151

AC XY:

11252

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.0370

Gnomad4 AMR

AF:

0.229

Gnomad4 ASJ

AF:

0.400

Gnomad4 EAS

AF:

0.383

Gnomad4 SAS

AF:

0.294

Gnomad4 FIN

AF:

0.144

Gnomad4 NFE

AF:

0.147

Gnomad4 OTH

AF:

0.209

Alfa

AF:

0.173

Hom.:

6127

Bravo

AF:

0.144

TwinsUK

AF:

0.108

AC:

399

ALSPAC

AF:

0.111

AC:

427

ESP6500AA

AF:

0.0313

AC:

138

ESP6500EA

AF:

0.154

AC:

1324

ExAC

AF:

0.201

AC:

24339

Asia WGS

AF:

0.321

AC:

1117

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 07, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Warburg micro syndrome 1

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -

Martsolf syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.051

T;.;.

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.066

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.86

D;D;D

MetaRNN

Benign

0.0039

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.92

L;L;.

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.60

N;N;N

REVEL

Benign

0.14

Sift

Benign

0.26

T;T;T

Sift4G

Benign

0.82

T;T;T

Polyphen

0.0010

B;.;.

Vest4

0.073

MPC

0.18

ClinPred

0.010

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.031

gMVP

0.084

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