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NM_000543.5(SMPD1):c.152A>T (p.Asp51Val) AND Sphingomyelin/cholesterol lipidosis

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
May 16, 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:
RCV003235590.1

Allele description [Variation Report for NM_000543.5(SMPD1):c.152A>T (p.Asp51Val)]

NM_000543.5(SMPD1):c.152A>T (p.Asp51Val)

Gene:
SMPD1:sphingomyelin phosphodiesterase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11p15.4
Genomic location:
Preferred name:
NM_000543.5(SMPD1):c.152A>T (p.Asp51Val)
HGVS:
  • NC_000011.10:g.6390750A>T
  • NG_011780.1:g.5326A>T
  • NM_000543.5:c.152A>TMANE SELECT
  • NM_001007593.3:c.152A>T
  • NM_001318087.2:c.152A>T
  • NM_001318088.2:c.-810A>T
  • NM_001365135.2:c.152A>T
  • NP_000534.3:p.Asp51Val
  • NP_001007594.2:p.Asp51Val
  • NP_001305016.1:p.Asp51Val
  • NP_001352064.1:p.Asp51Val
  • NC_000011.9:g.6411980A>T
  • NM_000543.4:c.152A>T
  • NR_027400.3:n.277A>T
  • NR_134502.2:n.277A>T
Protein change:
D51V
Links:
dbSNP: rs748589919
NCBI 1000 Genomes Browser:
rs748589919
Molecular consequence:
  • NM_001318088.2:c.-810A>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000543.5:c.152A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001007593.3:c.152A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001318087.2:c.152A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365135.2:c.152A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_027400.3:n.277A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_134502.2:n.277A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Sphingomyelin/cholesterol lipidosis
Synonyms:
Niemann-Pick disease
Identifiers:
MONDO: MONDO:0001982; MedGen: C0028064

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV003934636Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Likely pathogenic
(May 16, 2023)
germlineclinical testing

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

Citation Link

Summary from all submissions

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

Citations

PubMed

The demographics and distribution of type B Niemann-Pick disease: novel mutations lead to new genotype/phenotype correlations.

Simonaro CM, Desnick RJ, McGovern MM, Wasserstein MP, Schuchman EH.

Am J Hum Genet. 2002 Dec;71(6):1413-9. Epub 2002 Oct 4.

PubMed [citation]
PMID:
12369017
PMCID:
PMC378582

Acid sphingomyelinase deficiency: prevalence and characterization of an intermediate phenotype of Niemann-Pick disease.

Wasserstein MP, Aron A, Brodie SE, Simonaro C, Desnick RJ, McGovern MM.

J Pediatr. 2006 Oct;149(4):554-9.

PubMed [citation]
PMID:
17011332

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003934636.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

Variant summary: SMPD1 c.152A>T (p.Asp51Val) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 249640 control chromosomes. c.152A>T has been reported in the literature in individuals affected with Niemann-Pick Disease (Simonaro_2002, Wasserstein_2006), and these patients were reported as compound heterozygous with variants that may be pathogenic. These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 12369017, 17011332). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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

Last Updated: Jun 17, 2024