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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003934636	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (May 16, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 12369017, 17011332 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003934636

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(May 16, 2023)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

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

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

#	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

Last Updated: Jun 17, 2024

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