Submissions for variant NM_012233.3(RAB3GAP1):c.559C>T (p.Arg187Ter)

gnomAD frequency: 0.00001  dbSNP: rs764260054

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001858612	SCV002247231	pathogenic	not provided	2024-11-27	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg187*) 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 (rs764260054, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with clinical features of Warburg micro syndrome (PMID: 28454995, 29878067). ClinVar contains an entry for this variant (Variation ID: 800891). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV001858612	SCV003805282	pathogenic	not provided	2022-08-15	criteria provided, single submitter	clinical testing	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: 28454995, 29878067)
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV000985081	SCV004805023	pathogenic	Warburg micro syndrome 1	2024-03-17	criteria provided, single submitter	research
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City	RCV000985081	SCV001133041	likely pathogenic	Warburg micro syndrome 1	2019-09-26	no assertion criteria provided	clinical testing