chr1-220148325-TAAG-T

Position:

• chr1-220148325-TAAG-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_012414.4(RAB3GAP2):​c.*2923_*2925del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0573 in 152,876 control chromosomes in the GnomAD database, including 351 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.057 (351 hom., cov: 32)
  • Exomes 𝑓: 0.034 (0 hom.)
• Consequence: RAB3GAP2 NM_012414.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.526

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-220148325-TAAG-T is Benign according to our data. Variant chr1-220148325-TAAG-T is described in ClinVar as [Benign]. Clinvar id is 295602.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB3GAP2	NM_012414.4	c.*2923_*2925del		3_prime_UTR_variant	35/35	ENST00000358951.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB3GAP2	ENST00000358951.7	c.*2923_*2925del		3_prime_UTR_variant	35/35	1	NM_012414.4	P2

Frequencies

GnomAD3 genomes AF: 0.0573 AC: 8723 AN: 152140 Hom.: 351 Cov.: 32

Gnomad AFR AF: 0.0656

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0603

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.0588

Gnomad FIN AF: 0.0681

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0371

Gnomad OTH AF: 0.0617

GnomAD4 exome AF: 0.0340 AC: 21 AN: 618 Hom.: 0 AF XY: 0.0287 AC XY: 9 AN XY: 314

Gnomad4 AFR exome AF: 0.0938

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0290

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0574 AC: 8733 AN: 152258 Hom.: 351 Cov.: 32 AF XY: 0.0611 AC XY: 4547 AN XY: 74464

Gnomad4 AFR AF: 0.0657

Gnomad4 AMR AF: 0.0603

Gnomad4 ASJ AF: 0.0147

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.0586

Gnomad4 FIN AF: 0.0681

Gnomad4 NFE AF: 0.0371

Gnomad4 OTH AF: 0.0615

Alfa AF: 0.0110 Hom.: 3

Bravo AF: 0.0594

Asia WGS AF: 0.133 AC: 461 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Warburg micro syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Martsolf syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs3217443; hg19: chr1-220321667;