NM_000543.5(SMPD1):c.592G>C (p.Ala198Pro) AND Niemann-Pick disease, type B

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 21, 2019
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:: RCV001194004.9

Allele description [Variation Report for NM_000543.5(SMPD1):c.592G>C (p.Ala198Pro)]

NM_000543.5(SMPD1):c.592G>C (p.Ala198Pro)

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.592G>C (p.Ala198Pro)

HGVS:

NC_000011.10:g.6391657G>C
NG_011780.1:g.6233G>C
NM_000543.4(SMPD1):c.592G>C
NM_000543.5:c.592G>CMANE SELECT
NM_001007593.3:c.589G>C
NM_001318087.2:c.592G>C
NM_001318088.2:c.-370G>C
NM_001365135.2:c.592G>C
NP_000534.3:p.Ala198Pro
NP_000534.3:p.Ala198Pro
NP_001007594.2:p.Ala197Pro
NP_001305016.1:p.Ala198Pro
NP_001352064.1:p.Ala198Pro
NC_000011.9:g.6412887G>C
NM_000543.3:c.592G>C
NM_000543.4(SMPD1):c.592G>C
NM_000543.4:c.592G>C
NM_000543.5:c.592G>C
NR_027400.3:n.717G>C
p.Ala196Pro

Protein change:

A197P

Links:

dbSNP: rs797044798

NCBI 1000 Genomes Browser:

rs797044798

Molecular consequence:

NM_001318088.2:c.-370G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000543.5:c.592G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001007593.3:c.589G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001318087.2:c.592G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001365135.2:c.592G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_027400.3:n.717G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Niemann-Pick disease, type B
Identifiers:: MONDO: MONDO:0011871; MedGen: C0268243; Orphanet: 77293; OMIM: 607616

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001363222	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Jan 21, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 12369017, 15234149 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001363222

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Jan 21, 2019)

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

Ocular manifestations of Niemann-Pick disease type B.

McGovern MM, Wasserstein MP, Aron A, Desnick RJ, Schuchman EH, Brodie SE.

Ophthalmology. 2004 Jul;111(7):1424-7.

PubMed [citation]

PMID:: 15234149

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001363222.1

#	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.592G>C (p.Ala198Pro) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 212412 control chromosomes (gnomAD). c.592G>C has been reported in the literature in multiple individuals affected with Niemann-Pick disease type B (McGovern_2004, Simonaro_2002). These data indicate that the variant is very likely to be associated with disease. A ClinVar submission from a reputable database (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was 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

Last Updated: Nov 10, 2024

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