rs587777154

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5

The NM_012233.3(RAB3GAP1):c.52A>C(p.Thr18Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RAB3GAP1
NM_012233.3 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1O:1

Conservation

PhyloP100: 6.47

Publications

3 publications found

Variant links:

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

RAB3GAP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.902

PP5

Variant 2-135052463-A-C is Pathogenic according to our data. Variant chr2-135052463-A-C is described in ClinVar as Pathogenic. ClinVar VariationId is 100771.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012233.3. 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
	RAB3GAP1	NM_012233.3	MANE Select	c.52A>C	p.Thr18Pro	missense	Exon 2 of 24	NP_036365.1
	RAB3GAP1	NM_001172435.2		c.52A>C	p.Thr18Pro	missense	Exon 2 of 25	NP_001165906.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RAB3GAP1	ENST00000264158.13	TSL:1 MANE Select	c.52A>C	p.Thr18Pro	missense	Exon 2 of 24	ENSP00000264158.8
RAB3GAP1	ENST00000442034.5	TSL:1	c.52A>C	p.Thr18Pro	missense	Exon 2 of 25	ENSP00000411418.1
RAB3GAP1	ENST00000688182.1		c.52A>C	p.Thr18Pro	missense	Exon 2 of 5	ENSP00000509324.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461664

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727136

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5590

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112010

Other (OTH)

AF:

0.0000166

AC:

AN:

60370

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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Warburg micro syndrome 1

Pathogenic:1Other:1

May 01, 2013

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

GeneReviews

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.37

BayesDel_noAF

Pathogenic

0.30

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.70

Eigen

Pathogenic

0.73

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.85

M_CAP

Pathogenic

0.53

MetaRNN

Pathogenic

0.90

MetaSVM

Uncertain

0.037

MutationAssessor

Uncertain

2.8

PhyloP100

6.5

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-3.6

REVEL

Pathogenic

0.73

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.89

MutPred

0.65

Gain of phosphorylation at T15 (P = 0.0714)

MVP

0.82

MPC

0.94

ClinPred

0.99

GERP RS

4.4

PromoterAI

-0.074

Neutral

(source)

Varity_R

0.90

gMVP

0.91

Mutation Taster

=7/93

disease causing (ClinVar)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over