Variant chr2-135150276-T-C 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_012233.3(RAB3GAP1):c.1924-93T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0304 in 1,469,062 control chromosomes in the GnomAD database, including 2,042 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.040 ( 282 hom., cov: 32)

Exomes 𝑓: 0.029 ( 1760 hom. )

Consequence

RAB3GAP1
NM_012233.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.104

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:

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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 (BayesDel_noAF=-0.93).

BP6

Variant 2-135150276-T-C is Benign according to our data. Variant chr2-135150276-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 668610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB3GAP1	NM_012233.3 linkuse as main transcript	c.1924-93T>C		intron_variant		ENST00000264158.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB3GAP1	ENST00000264158.13 linkuse as main transcript	c.1924-93T>C		intron_variant		1	NM_012233.3	A1	Q15042-1

Frequencies

GnomAD3 genomes

AF:

0.0404

AC:

6153

AN:

152202

Hom.:

284

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0426

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.0841

Gnomad ASJ

AF:

0.0285

Gnomad EAS

AF:

0.182

Gnomad SAS

AF:

0.160

Gnomad FIN

AF:

0.0120

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0151

Gnomad OTH

AF:

0.0441

GnomAD4 exome

AF:

0.0292

AC:

38482

AN:

1316742

Hom.:

1760

AF XY:

0.0321

AC XY:

21256

AN XY:

661908

show subpopulations

Gnomad4 AFR exome

AF:

0.0454

Gnomad4 AMR exome

AF:

0.0867

Gnomad4 ASJ exome

AF:

0.0290

Gnomad4 EAS exome

AF:

0.154

Gnomad4 SAS exome

AF:

0.133

Gnomad4 FIN exome

AF:

0.0116

Gnomad4 NFE exome

AF:

0.0131

Gnomad4 OTH exome

AF:

0.0390

GnomAD4 genome

AF:

0.0404

AC:

6149

AN:

152320

Hom.:

282

Cov.:

AF XY:

0.0439

AC XY:

3273

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0427

Gnomad4 AMR

AF:

0.0837

Gnomad4 ASJ

AF:

0.0285

Gnomad4 EAS

AF:

0.182

Gnomad4 SAS

AF:

0.158

Gnomad4 FIN

AF:

0.0120

Gnomad4 NFE

AF:

0.0151

Gnomad4 OTH

AF:

0.0460

Alfa

AF:

0.0256

Hom.:

Bravo

AF:

0.0423

Asia WGS

AF:

0.165

AC:

574

AN:

3478

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

GeneDx

Jun 14, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

7.1

DANN

Benign

0.49

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