2-135052620-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_012233.3(RAB3GAP1):c.74+135C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00171 in 1,041,032 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0048 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (6 hom.)
• Consequence: RAB3GAP1 NM_012233.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.51

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 2-135052620-C-T is Benign according to our data. Variant chr2-135052620-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1214238.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00475 (724/152268) while in subpopulation AFR AF= 0.0146 (606/41548). AF 95% confidence interval is 0.0136. There are 2 homozygotes in gnomad4. There are 359 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB3GAP1	NM_012233.3	c.74+135C>T		intron_variant		ENST00000264158.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB3GAP1	ENST00000264158.13	c.74+135C>T		intron_variant		1	NM_012233.3	A1

Frequencies

GnomAD3 genomes AF: 0.00469 AC: 714 AN: 152150 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0144

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00366

Gnomad ASJ AF: 0.00951

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00335

GnomAD4 exome AF: 0.00118 AC: 1053 AN: 888764 Hom.: 6 AF XY: 0.00117 AC XY: 537 AN XY: 458248

Gnomad4 AFR exome AF: 0.0133

Gnomad4 AMR exome AF: 0.00147

Gnomad4 ASJ exome AF: 0.0171

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000284

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000351

Gnomad4 OTH exome AF: 0.00260

GnomAD4 genome AF: 0.00475 AC: 724 AN: 152268 Hom.: 2 Cov.: 32 AF XY: 0.00482 AC XY: 359 AN XY: 74444

Gnomad4 AFR AF: 0.0146

Gnomad4 AMR AF: 0.00366

Gnomad4 ASJ AF: 0.00951

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.000420 Hom.: 0

Bravo AF: 0.00566

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 16, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.017
Dann	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs150851637; hg19: chr2-135810190;