chr2-135067504-T-C

Variant names:

• chr2-135067504-T-C
• rs16831315
• NM_012233.3:c.150+9418T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012233.3(RAB3GAP1):​c.150+9418T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,214 control chromosomes in the GnomAD database, including 1,300 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1300 hom., cov: 32)
• Consequence: RAB3GAP1 NM_012233.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.983
• Publications: 11 publications found

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]

RAB3GAP1 Gene-Disease associations (from GenCC):

• Warburg micro syndrome

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Warburg micro syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• cataract-intellectual disability-hypogonadism syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB3GAP1	NM_012233.3	c.150+9418T>C		intron_variant	Intron 3 of 23	ENST00000264158.13	NP_036365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB3GAP1	ENST00000264158.13	c.150+9418T>C		intron_variant	Intron 3 of 23	1	NM_012233.3	ENSP00000264158.8

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17498 AN: 152096 Hom.: 1304 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0813

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.0627

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.0800

Gnomad OTH AF: 0.143

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.115 AC: 17506 AN: 152214 Hom.: 1300 Cov.: 32 AF XY: 0.120 AC XY: 8928 AN XY: 74410

African (AFR) AF: 0.111 AC: 4617 AN: 41510

American (AMR) AF: 0.201 AC: 3068 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 452 AN: 3470

East Asian (EAS) AF: 0.249 AC: 1285 AN: 5170

South Asian (SAS) AF: 0.319 AC: 1538 AN: 4826

European-Finnish (FIN) AF: 0.0627 AC: 665 AN: 10608

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.0800 AC: 5443 AN: 68016

Other (OTH) AF: 0.145 AC: 306 AN: 2114

Alfa AF: 0.0976 Hom.: 505

Bravo AF: 0.121

Asia WGS AF: 0.287 AC: 997 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.37
DANN	Benign	0.53
PhyloP100		-0.98
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16831315; hg19: chr2-135825074;