rs56786863

Variant names:

Variant summary

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

The NM_012233.3(RAB3GAP1):c.2290-17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0265 in 1,590,360 control chromosomes in the GnomAD database, including 1,430 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.061 ( 528 hom., cov: 32)

Exomes 𝑓: 0.023 ( 902 hom. )

Consequence

RAB3GAP1
NM_012233.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.67

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:

ZRANB3 (HGNC:25249): (zinc finger RANBP2-type containing 3) Enables ATP-dependent DNA/DNA annealing activity; K63-linked polyubiquitin modification-dependent protein binding activity; and endodeoxyribonuclease activity. Involved in several processes, including DNA metabolic process; DNA rewinding; and negative regulation of DNA recombination. Located in nuclear replication fork and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZRANB3 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 (BayesDel_noAF=-0.84).

BP6

Variant 2-135162538-C-T is Benign according to our data. Variant chr2-135162538-C-T is described in ClinVar as [Benign]. Clinvar id is 138860.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-135162538-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB3GAP1	NM_012233.3 link	c.2290-17C>T		intron_variant	Intron 19 of 23	ENST00000264158.13	NP_036365.1	Q15042-1B9A6J2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB3GAP1	ENST00000264158.13 link	c.2290-17C>T		intron_variant	Intron 19 of 23	1	NM_012233.3	ENSP00000264158.8		Q15042-1

Frequencies

GnomAD3 genomes

AF:

0.0606

AC:

9212

AN:

152008

Hom.:

528

Cov.:

show subpopulations

Gnomad AFR

AF:

0.153

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0421

Gnomad ASJ

AF:

0.0599

Gnomad EAS

AF:

0.0569

Gnomad SAS

AF:

0.0120

Gnomad FIN

AF:

0.0140

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.0211

Gnomad OTH

AF:

0.0535

GnomAD3 exomes

AF:

0.0346

AC:

8535

AN:

246450

Hom.:

312

AF XY:

0.0311

AC XY:

4133

AN XY:

133098

show subpopulations

Gnomad AFR exome

AF:

0.152

Gnomad AMR exome

AF:

0.0399

Gnomad ASJ exome

AF:

0.0661

Gnomad EAS exome

AF:

0.0490

Gnomad SAS exome

AF:

0.0121

Gnomad FIN exome

AF:

0.0178

Gnomad NFE exome

AF:

0.0207

Gnomad OTH exome

AF:

0.0307

GnomAD4 exome

AF:

0.0229

AC:

32889

AN:

1438234

Hom.:

902

Cov.:

AF XY:

0.0229

AC XY:

16397

AN XY:

716454

show subpopulations

Gnomad4 AFR exome

AF:

0.155

Gnomad4 AMR exome

AF:

0.0389

Gnomad4 ASJ exome

AF:

0.0702

Gnomad4 EAS exome

AF:

0.0536

Gnomad4 SAS exome

AF:

0.0120

Gnomad4 FIN exome

AF:

0.0176

Gnomad4 NFE exome

AF:

0.0166

Gnomad4 OTH exome

AF:

0.0317

GnomAD4 genome

AF:

0.0607

AC:

9229

AN:

152126

Hom.:

528

Cov.:

AF XY:

0.0587

AC XY:

4367

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.153

Gnomad4 AMR

AF:

0.0422

Gnomad4 ASJ

AF:

0.0599

Gnomad4 EAS

AF:

0.0570

Gnomad4 SAS

AF:

0.0120

Gnomad4 FIN

AF:

0.0140

Gnomad4 NFE

AF:

0.0211

Gnomad4 OTH

AF:

0.0539

Alfa

AF:

0.0501

Hom.:

Bravo

AF:

0.0669

Asia WGS

AF:

0.0330

AC:

116

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 15, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2014

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.18

DANN

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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