dbSNP rs35396665: RAB3GAP2:c.812-8_812-6delTTT (chr1-220196403-TAAA-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_012414.4(RAB3GAP2):c.812-8_812-6delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000831 in 1,203,172 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 21)

Exomes 𝑓: 8.3e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RAB3GAP2
NM_012414.4 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.214

Publications

0 publications found

Variant links:

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

RAB3GAP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB3GAP2	NM_012414.4 link	c.812-8_812-6delTTT		splice_region_variant, intron_variant	Intron 9 of 34	ENST00000358951.7	NP_036546.2	Q9H2M9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB3GAP2	ENST00000358951.7 link	c.812-8_812-6delTTT		splice_region_variant, intron_variant	Intron 9 of 34	1	NM_012414.4	ENSP00000351832.2		Q9H2M9-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

145694

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000616

AC:

AN:

162398

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000419

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

8.31e-7

AC:

AN:

1203172

Hom.:

AF XY:

0.00

AC XY:

AN XY:

601128

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27368

American (AMR)

AF:

0.0000260

AC:

AN:

38396

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21162

East Asian (EAS)

AF:

0.00

AC:

AN:

34406

South Asian (SAS)

AF:

0.00

AC:

AN:

72618

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4934

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

909506

Other (OTH)

AF:

0.00

AC:

AN:

50204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

145694

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

70764

African (AFR)

AF:

0.00

AC:

AN:

39624

American (AMR)

AF:

0.00

AC:

AN:

14700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3358

East Asian (EAS)

AF:

0.00

AC:

AN:

5074

South Asian (SAS)

AF:

0.00

AC:

AN:

4640

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9252

Middle Eastern (MID)

AF:

0.00

AC:

AN:

304

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65864

Other (OTH)

AF:

0.00

AC:

AN:

1984

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over