rs532964185
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_012233.3(RAB3GAP1):c.1039C>T(p.Arg347Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000205 in 1,612,304 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 (★★). Synonymous variant affecting the same amino acid position (i.e. R347R) has been classified as Benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_012233.3 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAB3GAP1 | NM_012233.3 | c.1039C>T | p.Arg347Ter | stop_gained | 12/24 | ENST00000264158.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAB3GAP1 | ENST00000264158.13 | c.1039C>T | p.Arg347Ter | stop_gained | 12/24 | 1 | NM_012233.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151614Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000319 AC: 8AN: 251176Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135738
GnomAD4 exome AF: 0.0000212 AC: 31AN: 1460572Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18AN XY: 726580
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151732Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74122
ClinVar
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Sep 16, 2022 | Nonsense variant predicted to result in protein truncation [or nonsense mediated decay] in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34169787, 31589614, 32740904, 23420520) - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 01, 2023 | This sequence change creates a premature translational stop signal (p.Arg347*) in the RAB3GAP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RAB3GAP1 are known to be pathogenic (PMID: 23420520). This variant is present in population databases (rs532964185, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with clinical features of Warburg Micro syndrome (PMID: 23420520). ClinVar contains an entry for this variant (Variation ID: 545410). For these reasons, this variant has been classified as Pathogenic. - |
Warburg micro syndrome 1 Pathogenic:1Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Pathogenic, criteria provided, single submitter | curation | Department Of Genetics, Sultan Qaboos University Hospital, Sultan Qaboos University | Dec 30, 2017 | - - |
Warburg micro syndrome 1;C5543626:Martsolf syndrome 2 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Feb 04, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at