rs760094551

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_012233.3(RAB3GAP1):​c.12C>G​(p.Asp4Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D4H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

RAB3GAP1
NM_012233.3 missense

Scores

2
4
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.92
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.36864552).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RAB3GAP1NM_012233.3 linkc.12C>G p.Asp4Glu missense_variant Exon 1 of 24 ENST00000264158.13 NP_036365.1 Q15042-1B9A6J2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RAB3GAP1ENST00000264158.13 linkc.12C>G p.Asp4Glu missense_variant Exon 1 of 24 1 NM_012233.3 ENSP00000264158.8 Q15042-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251476
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135918
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461630
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
727080
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.57
BayesDel_addAF
Benign
-0.067
T
BayesDel_noAF
Benign
-0.32
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.083
T;.;.
Eigen
Uncertain
0.38
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Benign
0.54
D
LIST_S2
Benign
0.80
T;T;T
M_CAP
Benign
0.041
D
MetaRNN
Benign
0.37
T;T;T
MetaSVM
Benign
-0.82
T
MutationAssessor
Benign
1.8
L;L;.
PrimateAI
Uncertain
0.72
T
PROVEAN
Benign
-0.78
N;N;N
REVEL
Benign
0.13
Sift
Pathogenic
0.0
D;D;D
Sift4G
Benign
0.14
T;T;D
Polyphen
1.0
D;.;.
Vest4
0.52
MutPred
0.11
Gain of glycosylation at P7 (P = 0.0828);Gain of glycosylation at P7 (P = 0.0828);Gain of glycosylation at P7 (P = 0.0828);
MVP
0.67
MPC
0.80
ClinPred
0.96
D
GERP RS
4.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8
Varity_R
0.62
gMVP
0.25

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs760094551; hg19: chr2-135809889; API