rs577915245
Positions:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_012233.3(RAB3GAP1):āc.724T>Cā(p.Tyr242His) variant causes a missense change. The variant allele was found at a frequency of 0.000151 in 1,611,872 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.000072 ( 1 hom., cov: 33)
Exomes š: 0.00016 ( 2 hom. )
Consequence
RAB3GAP1
NM_012233.3 missense
NM_012233.3 missense
Scores
5
14
Clinical Significance
Conservation
PhyloP100: 6.17
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.011078179).
BP6
?
Variant 2-135120894-T-C is Benign according to our data. Variant chr2-135120894-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 378451.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=3}.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00016 (233/1459658) while in subpopulation AMR AF= 0.00517 (231/44724). AF 95% confidence interval is 0.00462. There are 2 homozygotes in gnomad4_exome. There are 95 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAB3GAP1 | NM_012233.3 | c.724T>C | p.Tyr242His | missense_variant | 8/24 | ENST00000264158.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAB3GAP1 | ENST00000264158.13 | c.724T>C | p.Tyr242His | missense_variant | 8/24 | 1 | NM_012233.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152214Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.000811 AC: 204AN: 251414Hom.: 0 AF XY: 0.000611 AC XY: 83AN XY: 135880
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GnomAD4 exome AF: 0.000160 AC: 233AN: 1459658Hom.: 2 Cov.: 31 AF XY: 0.000131 AC XY: 95AN XY: 726258
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GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152214Hom.: 1 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74356
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 04, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 09, 2024 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 16, 2015 | - - |
RAB3GAP1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 12, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
B;.;.
Vest4
MutPred
Gain of disorder (P = 0.0646);Gain of disorder (P = 0.0646);.;
MVP
MPC
0.29
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at