NM_000543.5(SMPD1):c.1550A>T (p.Glu517Val) AND Sphingomyelin/cholesterol lipidosis

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 22, 2020
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:: RCV001249037.12

Allele description [Variation Report for NM_000543.5(SMPD1):c.1550A>T (p.Glu517Val)]

NM_000543.5(SMPD1):c.1550A>T (p.Glu517Val)

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.1550A>T (p.Glu517Val)

HGVS:

NC_000011.10:g.6394261A>T
NG_011780.1:g.8837A>T
NG_029615.1:g.30154T>A
NM_000543.5:c.1550A>TMANE SELECT
NM_001007593.3:c.1547A>T
NM_001318087.2:c.*43A>T
NM_001318088.2:c.629A>T
NM_001365135.2:c.1418A>T
NP_000534.3:p.Glu517Val
NP_001007594.2:p.Glu516Val
NP_001305017.1:p.Glu210Val
NP_001352064.1:p.Glu473Val
NC_000011.9:g.6415491A>T
NM_000543.4:c.1550A>T
NM_000543.5(SMPD1):c.1550A>TMANE SELECT
NR_027400.3:n.1503A>T
NR_134502.2:n.1042A>T
p.Glu517Val

Protein change:

E210V

Links:

dbSNP: rs142787001

NCBI 1000 Genomes Browser:

rs142787001

Molecular consequence:

NM_001318087.2:c.*43A>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000543.5:c.1550A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001007593.3:c.1547A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001318088.2:c.629A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001365135.2:c.1418A>T - missense variant - [Sequence Ontology: SO:0001583]
NR_027400.3:n.1503A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_134502.2:n.1042A>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

Recent activity

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LOW QUALITY PROTEIN: protein O-glucosyltransferase 1-like [Ostrea edulis]
LOW QUALITY PROTEIN: protein O-glucosyltransferase 1-like [Ostrea edulis]
gi|2507417378|ref|XP_048743702.2|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001422972	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 22, 2020)	germline	curation	PubMed (3) [See all records that cite these PMIDs] 26049896, 23430949, 25741868 Citation Link,
SCV001452643	Natera, Inc.	no assertion criteria provided	Uncertain significance (May 4, 2017)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001422972

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jan 22, 2020)

germline

curation

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

Citation Link,

SCV001452643

Natera, Inc.

no assertion criteria provided

Uncertain significance
(May 4, 2017)

germline

clinical testing

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, curation

Citations

PubMed

Successful within-patient dose escalation of olipudase alfa in acid sphingomyelinase deficiency.

Wasserstein MP, Jones SA, Soran H, Diaz GA, Lippa N, Thurberg BL, Culm-Merdek K, Shamiyeh E, Inguilizian H, Cox GF, Puga AC.

Mol Genet Metab. 2015 Sep-Oct;116(1-2):88-97. doi: 10.1016/j.ymgme.2015.05.013. Epub 2015 May 30.

PubMed [citation]

PMID:: 26049896
PMCID:: PMC4561589

Newborn screening for lysosomal storage disorders in hungary.

Wittmann J, Karg E, Turi S, Legnini E, Wittmann G, Giese AK, Lukas J, Gölnitz U, Klingenhäger M, Bodamer O, Mühl A, Rolfs A.

JIMD Rep. 2012;6:117-25. doi: 10.1007/8904_2012_130. Epub 2012 Mar 21.

PubMed [citation]

PMID:: 23430949
PMCID:: PMC3565645

See all PubMed Citations (3)

Details of each submission

From Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV001422972.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (3)

Description

The p.Glu517Val variant in SMPD1 (also known as p.Glu515Val due to a difference in cDNA numbering) has been reported in at least 2 individuals with Niemann-Pick disease (PMID: 23430949, 26049896) and has been identified in 0.410% (529/129080) of European (non-Finnish) chromosomes, including 2 homozygotes, 0.192% (68/35430) of Latino chromosomes, and 0.108% (27/24970) of African chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs142787001). This variant has also been reported in ClinVar (VariationID: 198094) as likely benign by EGL Genetic Diagnostics and as a VUS by ARUP Laboratories and Integrated Genetics. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. The presence of this variant in combination with a reported pathogenic variant and in an individual with Niemann-Pick disease increases the likelihood that the p.Glu517Val variant is pathogenic (VariationID: 2994; PMID: 23430949). In summary, the clinical significance of the p.Glu517Val variant is uncertain. ACMG/AMP Criteria applied: BS1, PP3, PM3_Supporting (Richards 2015).

#	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 Natera, Inc., SCV001452643.1

#	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

Last Updated: Nov 10, 2024

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