NM_000543.5(SMPD1):c.475T>C (p.Cys159Arg) AND Niemann-Pick disease, type A

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Mar 26, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000153979.16

Allele description [Variation Report for NM_000543.5(SMPD1):c.475T>C (p.Cys159Arg)]

NM_000543.5(SMPD1):c.475T>C (p.Cys159Arg)

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.475T>C (p.Cys159Arg)

HGVS:

NC_000011.10:g.6391540T>C
NG_011780.1:g.6116T>C
NM_000543.5:c.475T>CMANE SELECT
NM_001007593.3:c.472T>C
NM_001318087.2:c.475T>C
NM_001318088.2:c.-487T>C
NM_001365135.2:c.475T>C
NP_000534.3:p.Cys159Arg
NP_000534.3:p.Cys159Arg
NP_001007594.2:p.Cys158Arg
NP_001305016.1:p.Cys159Arg
NP_001352064.1:p.Cys159Arg
NC_000011.9:g.6412770T>C
NM_000543.4(SMPD1):c.475T>C
NM_000543.4:c.475T>C
NR_027400.3:n.600T>C

Protein change:

C158R

Links:

dbSNP: rs727504166

NCBI 1000 Genomes Browser:

rs727504166

Molecular consequence:

NM_001318088.2:c.-487T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000543.5:c.475T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001007593.3:c.472T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001318087.2:c.475T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001365135.2:c.475T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_027400.3:n.600T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Niemann-Pick disease, type A
Synonyms:: SPHINGOMYELIN LIPIDOSIS; SPHINGOMYELINASE DEFICIENCY
Identifiers:: MONDO: MONDO:0009756; MedGen: C0268242; Orphanet: 77292; OMIM: 257200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000793590	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Likely pathogenic (Aug 22, 2017)	unknown	clinical testing	PubMed (4) [See all records that cite these PMIDs] 8407868, 27725636, 17011332, 16434659 Citation Link,
SCV002091679	Natera, Inc.	no assertion criteria provided	Likely pathogenic (Sep 21, 2020)	germline	clinical testing
SCV004205059	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 26, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000793590

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Likely pathogenic
(Aug 22, 2017)

unknown

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link,

SCV002091679

Natera, Inc.

no assertion criteria provided

Likely pathogenic
(Sep 21, 2020)

germline

clinical testing

SCV004205059

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 26, 2024)

unknown

clinical testing

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

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Cloning of a human acid sphingomyelinase cDNA with a new mutation that renders the enzyme inactive.

Ida H, Rennert OM, Eto Y, Chan WY.

J Biochem. 1993 Jul;114(1):15-20.

PubMed [citation]

PMID:: 8407868

Human acid sphingomyelinase structures provide insight to molecular basis of Niemann-Pick disease.

Zhou YF, Metcalf MC, Garman SC, Edmunds T, Qiu H, Wei RR.

Nat Commun. 2016 Oct 11;7:13082. doi: 10.1038/ncomms13082.

PubMed [citation]

PMID:: 27725636
PMCID:: PMC5062611

See all PubMed Citations (5)

Details of each submission

From Counsyl, SCV000793590.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Natera, Inc., SCV002091679.1

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

#	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

From Baylor Genetics, SCV004205059.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 26, 2024

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