NM_012414.4:c.116-4241T>A

Variant names:

• chr1-220237104-A-T
• rs10495145
• NM_012414.4:c.116-4241T>A

Variant summary

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

The NM_012414.4(RAB3GAP2):​c.116-4241T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0414 in 152,276 control chromosomes in the GnomAD database, including 273 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 0.041 (273 hom., cov: 32)
• Consequence: RAB3GAP2 NM_012414.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.257
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Martsolf syndrome 1

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• RAB18 deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics
• Warburg micro syndrome

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Warburg micro syndrome 2

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• autosomal recessive spastic paraplegia type 69

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012414.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB3GAP2	NM_012414.4	MANE Select	c.116-4241T>A		intron	N/A	NP_036546.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB3GAP2	ENST00000358951.7	TSL:1 MANE Select	c.116-4241T>A		intron	N/A	ENSP00000351832.2
	RAB3GAP2	ENST00000692972.1		c.116-4241T>A		intron	N/A	ENSP00000510753.1
	RAB3GAP2	ENST00000691661.1		c.116-4241T>A		intron	N/A	ENSP00000510185.1

Frequencies

GnomAD3 genomes AF: 0.0414 AC: 6299 AN: 152158 Hom.: 272 Cov.: 32

Gnomad AFR AF: 0.0752

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0515

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.0465

Gnomad FIN AF: 0.0107

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0130

Gnomad OTH AF: 0.0411

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

GnomAD4 genome AF: 0.0414 AC: 6305 AN: 152276 Hom.: 273 Cov.: 32 AF XY: 0.0420 AC XY: 3124 AN XY: 74462

African (AFR) AF: 0.0750 AC: 3117 AN: 41544

American (AMR) AF: 0.0520 AC: 795 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3470

East Asian (EAS) AF: 0.201 AC: 1037 AN: 5168

South Asian (SAS) AF: 0.0462 AC: 223 AN: 4830

European-Finnish (FIN) AF: 0.0107 AC: 114 AN: 10614

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0130 AC: 882 AN: 68032

Other (OTH) AF: 0.0402 AC: 85 AN: 2112

Alfa AF: 0.0244 Hom.: 11

Bravo AF: 0.0480

Asia WGS AF: 0.105 AC: 362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.3
DANN	Benign	0.68
PhyloP100		0.26
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: rs10495145; hg19: chr1-220410446;