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NM_019892.6(INPP5E):c.1132C>T (p.Arg378Cys) AND INPP5E-related condition

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Feb 1, 2024
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV003904789.1

Allele description [Variation Report for NM_019892.6(INPP5E):c.1132C>T (p.Arg378Cys)]

NM_019892.6(INPP5E):c.1132C>T (p.Arg378Cys)

Gene:
INPP5E:inositol polyphosphate-5-phosphatase E [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q34.3
Genomic location:
Preferred name:
NM_019892.6(INPP5E):c.1132C>T (p.Arg378Cys)
HGVS:
  • NC_000009.12:g.136433182G>A
  • NG_016126.1:g.11623C>T
  • NM_001318502.2:c.1132C>T
  • NM_019892.6:c.1132C>TMANE SELECT
  • NP_001305431.1:p.Arg378Cys
  • NP_063945.2:p.Arg378Cys
  • NC_000009.11:g.139327634G>A
  • NM_019892.4:c.1132C>T
  • NM_019892.5:c.1132C>T
  • Q9NRR6:p.Arg378Cys
Protein change:
R378C; ARG378CYS
Links:
UniProtKB: Q9NRR6#VAR_063012; OMIM: 613037.0005; dbSNP: rs121918130
NCBI 1000 Genomes Browser:
rs121918130
Molecular consequence:
  • NM_001318502.2:c.1132C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_019892.6:c.1132C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
INPP5E-related condition
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004725077PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Feb 1, 2024) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004725077.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

The INPP5E c.1132C>T variant is predicted to result in the amino acid substitution p.Arg378Cys. This variant has been reported in the homozygous state in two related individuals with Joubert Syndrome; an in vitro enzymatic assay in this same study showed the p.Arg378Cys variant has impaired 5-phosphatase activity compared to wildtype (Bielas et al 2009. PubMed ID: 19668216). This variant has also been reported in an additional individual with retinal disease (Table S1, Karali et al. 2022. PubMed ID: 36460718). This variant is reported in 0.021% of alleles in individuals of African descent in gnomAD. A different substitution of this amino acid (p.Arg378His) has also been reported in the compound heterozygous state in an individual with Leber congenital amaurosis (Porto et al. 2017. PubMed ID: 29186038). Given the evidence, we interpret c.1132C>T (p.Arg378Cys) as likely pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 15, 2024