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NM_019892.6(INPP5E):c.746C>T (p.Ser249Phe) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Mar 21, 2023
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:
RCV003226465.1

Allele description [Variation Report for NM_019892.6(INPP5E):c.746C>T (p.Ser249Phe)]

NM_019892.6(INPP5E):c.746C>T (p.Ser249Phe)

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.746C>T (p.Ser249Phe)
HGVS:
  • NC_000009.12:g.136438674G>A
  • NG_016126.1:g.6131C>T
  • NM_001318502.2:c.746C>T
  • NM_019892.6:c.746C>TMANE SELECT
  • NP_001305431.1:p.Ser249Phe
  • NP_063945.2:p.Ser249Phe
  • NC_000009.11:g.139333126G>A
  • NM_019892.4:c.746C>T
  • NM_019892.5:c.746C>T
Protein change:
S249F
Links:
dbSNP: rs550485638
NCBI 1000 Genomes Browser:
rs550485638
Molecular consequence:
  • NM_001318502.2:c.746C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_019892.6:c.746C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003923139Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Uncertain significance
(Mar 21, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

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

Citations

PubMed

Lysoplex: An efficient toolkit to detect DNA sequence variations in the autophagy-lysosomal pathway.

Di Fruscio G, Schulz A, De Cegli R, Savarese M, Mutarelli M, Parenti G, Banfi S, Braulke T, Nigro V, Ballabio A.

Autophagy. 2015;11(6):928-38. doi: 10.1080/15548627.2015.1043077.

PubMed [citation]
PMID:
26075876
PMCID:
PMC4502703

Next generation sequencing based identification of disease-associated mutations in Swiss patients with retinal dystrophies.

Tiwari A, Bahr A, Bähr L, Fleischhauer J, Zinkernagel MS, Winkler N, Barthelmes D, Berger L, Gerth-Kahlert C, Neidhardt J, Berger W.

Sci Rep. 2016 Jun 29;6:28755. doi: 10.1038/srep28755.

PubMed [citation]
PMID:
27353947
PMCID:
PMC4926080
See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003923139.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

Variant summary: INPP5E c.746C>T (p.Ser249Phe) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 7.3e-05 in 206804 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in INPP5E causing Joubert Syndrome And Related Disorders (7.3e-05 vs 0.00079), allowing no conclusion about variant significance. c.746C>T has been reported in the literature in individuals affected with Joubert Syndrome Related Disorders. These reports do not provide unequivocal conclusions about association of the variant with Joubert Syndrome And Related Disorders. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (likely pathogenic n=1, VUS n=3). Based on the evidence outlined above, the variant was classified as uncertain significance.

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

Last Updated: May 25, 2025