NM_000543.5(SMPD1):c.955G>C (p.Gly319Arg) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 20, 2023
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:: RCV003767992.2

Allele description [Variation Report for NM_000543.5(SMPD1):c.955G>C (p.Gly319Arg)]

NM_000543.5(SMPD1):c.955G>C (p.Gly319Arg)

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.955G>C (p.Gly319Arg)

HGVS:

NC_000011.10:g.6392020G>C
NG_011780.1:g.6596G>C
NM_000543.4:c.[955G>C]
NM_000543.5:c.955G>CMANE SELECT
NM_001007593.3:c.952G>C
NM_001318087.2:c.955G>C
NM_001318088.2:c.-7G>C
NM_001365135.2:c.955G>C
NP_000534.3:p.Gly319Arg
NP_001007594.2:p.Gly318Arg
NP_001305016.1:p.Gly319Arg
NP_001352064.1:p.Gly319Arg
NC_000011.9:g.6413250G>C
NM_000543.4:c.955G>C
NM_000543.4:c.[955G>C]
NM_000543.5:c.955G>C
NR_027400.3:n.1080G>C

Protein change:

G318R

Links:

dbSNP: rs757934797

NCBI 1000 Genomes Browser:

rs757934797

Molecular consequence:

NM_001318088.2:c.-7G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000543.5:c.955G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001007593.3:c.952G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001318087.2:c.955G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001365135.2:c.955G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_027400.3:n.1080G>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

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

Recent activity

Clear Turn Off Turn On

kallikrein-13 isoform 1 precursor [Homo sapiens]
kallikrein-13 isoform 1 precursor [Homo sapiens]
gi|11496281|ref|NP_056411.1|

Protein

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004570145	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 20, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 34273913, 27338287, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004570145

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 20, 2023)

germline

clinical testing

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

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

Functional characterization of novel variants in SMPD1 in Indian patients with acid sphingomyelinase deficiency.

Deshpande D, Gupta SK, Sarma AS, Ranganath P, Jain S JMN, Sheth J, Mistri M, Gupta N, Kabra M, Phadke SR, Girisha KM, Dua Puri R, Aggarwal S, Datar C, Mandal K, Tilak P, Muranjan M, Bijarnia-Mahay S, Rama Devi A R, Tayade NB, Ranjan A, Dalal AB.

Hum Mutat. 2021 Oct;42(10):1336-1350. doi: 10.1002/humu.24263. Epub 2021 Aug 3.

PubMed [citation]

PMID:: 34273913

Spectrum of SMPD1 mutations in Asian-Indian patients with acid sphingomyelinase (ASM)-deficient Niemann-Pick disease.

Ranganath P, Matta D, Bhavani GS, Wangnekar S, Jain JM, Verma IC, Kabra M, Puri RD, Danda S, Gupta N, Girisha KM, Sankar VH, Patil SJ, Ramadevi AR, Bhat M, Gowrishankar K, Mandal K, Aggarwal S, Tamhankar PM, Tilak P, Phadke SR, Dalal A.

Am J Med Genet A. 2016 Oct;170(10):2719-30. doi: 10.1002/ajmg.a.37817. Epub 2016 Jun 24.

PubMed [citation]

PMID:: 27338287

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004570145.1

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

Description

Experimental studies have shown that this missense change affects SMPD1 function (PMID: 34273913). For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SMPD1 protein function. ClinVar contains an entry for this variant (Variation ID: 555444). This missense change has been observed in individual(s) with Niemann-Pick disease type A (PMID: 27338287). This variant is present in population databases (rs757934797, gnomAD 0.0009%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 319 of the SMPD1 protein (p.Gly319Arg).

#	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

ClinVar

Relating variation to medicine