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

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP6_ModerateBS1

The NM_012414.4(RAB3GAP2):c.812-6dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0402 in 1,175,140 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 21)

Exomes 𝑓: 0.046 ( 0 hom. )

Consequence

RAB3GAP2
NM_012414.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

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:

RAB3GAP2 (HGNC:):

RAB3GAP2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 1-220196403-T-TA is Benign according to our data. Variant chr1-220196403-T-TA is described in ClinVar as [Benign]. Clinvar id is 1575669.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0458 (47162/1029514) while in subpopulation NFE AF= 0.0479 (37274/778602). AF 95% confidence interval is 0.0475. There are 0 homozygotes in gnomad4_exome. There are 22795 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB3GAP2	NM_012414.4 linkuse as main transcript	c.812-6dupT		splice_region_variant, intron_variant		ENST00000358951.7	NP_036546.2	Q9H2M9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB3GAP2	ENST00000358951.7 linkuse as main transcript	c.812-6dupT		splice_region_variant, intron_variant		1	NM_012414.4	ENSP00000351832.2		Q9H2M9-1

Frequencies

GnomAD3 genomes

AF:

0.000419

AC:

AN:

145564

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000404

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000197

Gnomad SAS

AF:

0.00129

Gnomad FIN

AF:

0.00152

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000365

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0458

AC:

47162

AN:

1029514

Hom.:

Cov.:

AF XY:

0.0446

AC XY:

22795

AN XY:

511182

show subpopulations

Gnomad4 AFR exome

AF:

0.0462

Gnomad4 AMR exome

AF:

0.0259

Gnomad4 ASJ exome

AF:

0.0658

Gnomad4 EAS exome

AF:

0.0273

Gnomad4 SAS exome

AF:

0.0415

Gnomad4 FIN exome

AF:

0.0348

Gnomad4 NFE exome

AF:

0.0479

Gnomad4 OTH exome

AF:

0.0468

GnomAD4 genome

AF:

0.000433

AC:

AN:

145626

Hom.:

Cov.:

AF XY:

0.000438

AC XY:

AN XY:

70772

show subpopulations

Gnomad4 AFR

AF:

0.000453

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000198

Gnomad4 SAS

AF:

0.00130

Gnomad4 FIN

AF:

0.00152

Gnomad4 NFE

AF:

0.000365

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Martsolf syndrome;C3280214:Warburg micro syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 11, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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