Variant 1-220196403-TAA-TA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_012414.4(RAB3GAP2):c.812-6del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 1,241,496 control chromosomes in the GnomAD database, including 21,623 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5009 hom., cov: 21)

Exomes 𝑓: 0.29 ( 16614 hom. )

Consequence

RAB3GAP2
NM_012414.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.00300

Variant links:

Genes affected

RAB3GAP2 (HGNC:17168): (RAB3 GTPase activating non-catalytic protein subunit 2) The protein encoded by this gene belongs to the RAB3 protein family, members of which are involved in regulated exocytosis of neurotransmitters and hormones. This protein forms the Rab3 GTPase-activating complex with RAB3GAP1, where it constitutes the regulatory subunit, whereas the latter functions as the catalytic subunit. This gene has the highest level of expression in the brain, consistent with it having a key role in neurodevelopment. Mutations in this gene are associated with Martsolf syndrome.[provided by RefSeq, Oct 2009]

RAB3GAP2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 1-220196403-TA-T is Benign according to our data. Variant chr1-220196403-TA-T is described in ClinVar as [Benign]. Clinvar id is 295665.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-220196403-TA-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB3GAP2	NM_012414.4 linkuse as main transcript	c.812-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000358951.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB3GAP2	ENST00000358951.7 linkuse as main transcript	c.812-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_012414.4	P2	Q9H2M9-1

Frequencies

GnomAD3 genomes

AF:

0.265

AC:

38504

AN:

145470

Hom.:

5003

Cov.:

show subpopulations

Gnomad AFR

AF:

0.257

Gnomad AMI

AF:

0.299

Gnomad AMR

AF:

0.322

Gnomad ASJ

AF:

0.143

Gnomad EAS

AF:

0.390

Gnomad SAS

AF:

0.244

Gnomad FIN

AF:

0.312

Gnomad MID

AF:

0.204

Gnomad NFE

AF:

0.248

Gnomad OTH

AF:

0.239

GnomAD4 exome

AF:

0.293

AC:

320888

AN:

1095966

Hom.:

16614

Cov.:

AF XY:

0.292

AC XY:

159599

AN XY:

546122

show subpopulations

Gnomad4 AFR exome

AF:

0.300

Gnomad4 AMR exome

AF:

0.415

Gnomad4 ASJ exome

AF:

0.222

Gnomad4 EAS exome

AF:

0.383

Gnomad4 SAS exome

AF:

0.299

Gnomad4 FIN exome

AF:

0.335

Gnomad4 NFE exome

AF:

0.283

Gnomad4 OTH exome

AF:

0.297

GnomAD4 genome

AF:

0.265

AC:

38541

AN:

145530

Hom.:

5009

Cov.:

AF XY:

0.269

AC XY:

19037

AN XY:

70706

show subpopulations

Gnomad4 AFR

AF:

0.258

Gnomad4 AMR

AF:

0.322

Gnomad4 ASJ

AF:

0.143

Gnomad4 EAS

AF:

0.390

Gnomad4 SAS

AF:

0.244

Gnomad4 FIN

AF:

0.312

Gnomad4 NFE

AF:

0.248

Gnomad4 OTH

AF:

0.242

Bravo

AF:

0.261

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Warburg micro syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Martsolf syndrome;C3280214:Warburg micro syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Martsolf syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 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

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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