NM_000543.5(SMPD1):c.1493G>T (p.Arg498Leu) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Dec 5, 2022
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:: RCV000413382.19

Allele description [Variation Report for NM_000543.5(SMPD1):c.1493G>T (p.Arg498Leu)]

NM_000543.5(SMPD1):c.1493G>T (p.Arg498Leu)

Genes:

APBB1:amyloid beta precursor protein binding family B member 1 [Gene - OMIM - HGNC]
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.1493G>T (p.Arg498Leu)

Other names:

R496L

HGVS:

NC_000011.10:g.6394204G>T
NG_011780.1:g.8780G>T
NG_029615.1:g.30211C>A
NM_000543.4(SMPD1):c.1493G>T
NM_000543.5:c.1493G>TMANE SELECT
NM_001007593.3:c.1490G>T
NM_001318087.2:c.1513G>T
NM_001318088.2:c.572G>T
NM_001365135.2:c.1361G>T
NP_000534.3:p.Arg498Leu
NP_000534.3:p.Arg498Leu
NP_001007594.2:p.Arg497Leu
NP_001305016.1:p.Val505Leu
NP_001305017.1:p.Arg191Leu
NP_001352064.1:p.Arg454Leu
NC_000011.9:g.6415434G>T
NM_000543.3:c.1493G>T
NM_000543.4(SMPD1):c.1493G>T
NM_000543.4:c.1493G>T
NR_027400.3:n.1446G>T
NR_134502.2:n.985G>T
c.1493G>T (p.Arg498Leu)
p.Arg496Leu

Protein change:

R191L; ARG496LEU

Links:

OMIM: 607608.0001; dbSNP: rs120074117

NCBI 1000 Genomes Browser:

rs120074117

Molecular consequence:

NM_000543.5:c.1493G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001007593.3:c.1490G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001318087.2:c.1513G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001318088.2:c.572G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001365135.2:c.1361G>T - missense variant - [Sequence Ontology: SO:0001583]
NR_027400.3:n.1446G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_134502.2:n.985G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000231559	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Apr 6, 2015)	germline	clinical testing	Citation Link,
SCV000490819	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jun 29, 2020)	germline	clinical testing	Citation Link,
SCV002020769	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Dec 5, 2022)	germline	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

SCV000231559

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Pathogenic
(Apr 6, 2015)

germline

clinical testing

Citation Link,

SCV000490819

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jun 29, 2020)

germline

clinical testing

Citation Link,

SCV002020769

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Dec 5, 2022)

germline

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	13	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	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

Details of each submission

From Eurofins Ntd Llc (ga), SCV000231559.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	13	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		13	not provided	not provided	not provided

From GeneDx, SCV000490819.2

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

Description

Common pathogenic variant in Ashkenazi Jewish patients with neuronopathic acid sphingomyelinase deficiency, also known as Niemann-Pick disease, type A (Levran et al., 1991); Functional studies found R498L is associated with less than 2% of wild-type enzyme activity (Jones et al., 2008); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 1885770, 18815062, 21228398, 2023926, 15221801, 26169695, 30153451, 21502868, 1391960, 26320887)

#	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 Revvity Omics, Revvity, SCV002020769.3

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

Last Updated: Sep 29, 2024

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