NM_012233.3(RAB3GAP1):c.1039C>T (p.Arg347Ter) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 1, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001855346.14

Allele description [Variation Report for NM_012233.3(RAB3GAP1):c.1039C>T (p.Arg347Ter)]

NM_012233.3(RAB3GAP1):c.1039C>T (p.Arg347Ter)

Gene:

RAB3GAP1:RAB3 GTPase activating protein catalytic subunit 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q21.3

Genomic location:

Preferred name:

NM_012233.3(RAB3GAP1):c.1039C>T (p.Arg347Ter)

HGVS:

NC_000002.12:g.135130060C>T
NG_016972.1:g.82796C>T
NM_001172435.2:c.1039C>T
NM_012233.3:c.1039C>TMANE SELECT
NP_001165906.1:p.Arg347Ter
NP_036365.1:p.Arg347Ter
NP_036365.1:p.Arg347Ter
NC_000002.11:g.135887630C>T
NM_012233.2:c.1039C>T

Protein change:

R347*

Links:

dbSNP: rs532964185

NCBI 1000 Genomes Browser:

rs532964185

Molecular consequence:

NM_001172435.2:c.1039C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_012233.3:c.1039C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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sin3 histone deacetylase corepressor complex component SDS3 isoform X4 [Homo sap...
sin3 histone deacetylase corepressor complex component SDS3 isoform X4 [Homo sapiens]
gi|2462533720|ref|XP_054228876.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002234646	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 1, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23420520, 28492532
SCV003842415	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Sep 16, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002234646

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 1, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV003842415

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Sep 16, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutation spectrum in RAB3GAP1, RAB3GAP2, and RAB18 and genotype-phenotype correlations in warburg micro syndrome and Martsolf syndrome.

Handley MT, Morris-Rosendahl DJ, Brown S, Macdonald F, Hardy C, Bem D, Carpanini SM, Borck G, Martorell L, Izzi C, Faravelli F, Accorsi P, Pinelli L, Basel-Vanagaite L, Peretz G, Abdel-Salam GM, Zaki MS, Jansen A, Mowat D, Glass I, Stewart H, Mancini G, et al.

Hum Mutat. 2013 May;34(5):686-96. doi: 10.1002/humu.22296.

PubMed [citation]

PMID:: 23420520

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV002234646.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneDx, SCV003842415.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

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)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 2, 2024

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