NM_000543.5(SMPD1):c.1474G>A (p.Gly492Ser) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (5 submissions)
Last evaluated:: Oct 1, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV000514622.14

Allele description [Variation Report for NM_000543.5(SMPD1):c.1474G>A (p.Gly492Ser)]

NM_000543.5(SMPD1):c.1474G>A (p.Gly492Ser)

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.1474G>A (p.Gly492Ser)

HGVS:

NC_000011.10:g.6394029G>A
NG_011780.1:g.8605G>A
NG_029615.1:g.30386C>T
NM_000543.5:c.1474G>AMANE SELECT
NM_001007593.3:c.1471G>A
NM_001318087.2:c.1474G>A
NM_001318088.2:c.553G>A
NM_001365135.2:c.1342G>A
NP_000534.3:p.Gly492Ser
NP_001007594.2:p.Gly491Ser
NP_001305016.1:p.Gly492Ser
NP_001305017.1:p.Gly185Ser
NP_001352064.1:p.Gly448Ser
NC_000011.9:g.6415259G>A
NM_000543.4(SMPD1):c.1474G>A
NM_000543.4:c.1474G>A
NR_027400.3:n.1427G>A
NR_134502.2:n.946G>A
p.Gly492Ser

Protein change:

G185S

Links:

dbSNP: rs144873307

NCBI 1000 Genomes Browser:

rs144873307

Molecular consequence:

NM_000543.5:c.1474G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001007593.3:c.1471G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001318087.2:c.1474G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001318088.2:c.553G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365135.2:c.1342G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_027400.3:n.1427G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_134502.2:n.946G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000610587	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jun 12, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000702522	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL ClinVar v180209 classification definitions)	Uncertain significance (Jul 17, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV000801068	Mayo Clinic Laboratories, Mayo Clinic	no assertion criteria provided	Uncertain significance (Jul 18, 2017)	unknown	clinical testing
SCV001784836	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Aug 8, 2022)	germline	clinical testing	Citation Link,
SCV005431598	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Likely benign (Oct 1, 2024)	germline	clinical testing	Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	5	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
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Identification of seven novel SMPD1 mutations causing Niemann-Pick disease types A and B.

Irun P, Mallén M, Dominguez C, Rodriguez-Sureda V, Alvarez-Sala LA, Arslan N, Bermejo N, Guerrero C, Perez de Soto I, Villalón L, Giraldo P, Pocovi M.

Clin Genet. 2013 Oct;84(4):356-61. doi: 10.1111/cge.12076. Epub 2013 Jan 4.

PubMed [citation]

PMID:: 23252888

Details of each submission

From Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics, SCV000610587.1

#	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	germline	not provided	not provided	not provided	not provided		not provided	0.000971	not provided	not provided

From Eurofins Ntd Llc (ga), SCV000702522.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	5	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	germline	unknown	not provided	not provided	not provided		5	not provided	not provided	not provided

From Mayo Clinic Laboratories, Mayo Clinic, SCV000801068.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneDx, SCV001784836.3

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

Description

Reported in a patient with Parkinson disease in published literature; however, additional segregation information was not provided (Alcalay et al., 2019); Reported in the heterozygous state in a patient with a suspected lysosomal storage disease in published literature; however, the patient also harbored variants in other genes (Wang et al., 2017); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 23252888, 28703315, 30788890, 26499107, 25933391, 34426522)

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

From CeGaT Center for Human Genetics Tuebingen, SCV005431598.1

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

Description

SMPD1: BP4

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

Last Updated: Dec 22, 2024

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