1-220148738-C-CT

Position:

• chr1-220148738-C-CT

Variant summary

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

The NM_012414.4(RAB3GAP2):​c.*2512_*2513insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0427 in 151,492 control chromosomes in the GnomAD database, including 455 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.043 (455 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: RAB3GAP2 NM_012414.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -1.83

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 1-220148738-C-CT is Benign according to our data. Variant chr1-220148738-C-CT is described in ClinVar as [Likely_benign]. Clinvar id is 295608.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB3GAP2	NM_012414.4	c.*2512_*2513insA		3_prime_UTR_variant	35/35	ENST00000358951.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB3GAP2	ENST00000358951.7	c.*2512_*2513insA		3_prime_UTR_variant	35/35	1	NM_012414.4	P2

Frequencies

GnomAD3 genomes AF: 0.0428 AC: 6472 AN: 151382 Hom.: 454 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0166

Gnomad ASJ AF: 0.0162

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000627

Gnomad FIN AF: 0.000191

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000590

Gnomad OTH AF: 0.0256

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0427 AC: 6467 AN: 151492 Hom.: 455 Cov.: 32 AF XY: 0.0423 AC XY: 3129 AN XY: 74036

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.0166

Gnomad4 ASJ AF: 0.0162

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000418

Gnomad4 FIN AF: 0.000191

Gnomad4 NFE AF: 0.000590

Gnomad4 OTH AF: 0.0253

Bravo AF: 0.0489

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Warburg micro syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Martsolf syndrome Benign:1

Likely 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: rs143756119; hg19: chr1-220322080;