NM_000543.5(SMPD1):c.955G>C (p.Gly319Arg) AND Niemann-Pick disease, type B

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Sep 1, 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:: RCV001527420.3

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]

Observations:

Condition(s)

Name:: Niemann-Pick disease, type B
Identifiers:: MONDO: MONDO:0011871; MedGen: C0268243; Orphanet: 77293; OMIM: 607616

Recent activity

Clear Turn Off Turn On

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
SCV001738420	Diagnostics Division, CENTRE FOR DNA FINGERPRINTING AND DIAGNOSTICS	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 25, 2021)	germline	research	PubMed (1) [See all records that cite this PMID]
SCV002572578	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Sep 1, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27338287, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001738420

Diagnostics Division, CENTRE FOR DNA FINGERPRINTING AND DIAGNOSTICS

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Apr 25, 2021)

germline

research

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

SCV002572578

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Sep 1, 2022)

germline

clinical testing

PubMed (2)
[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	yes	2	not provided	not provided	2	not provided	research, clinical testing

Citations

PubMed

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

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 Diagnostics Division, CENTRE FOR DNA FINGERPRINTING AND DIAGNOSTICS, SCV001738420.1

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

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

From 3billion, SCV002572578.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (2)

Description

The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: <0.001%). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.98; 3Cnet: 1.00). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with SMPD1-related disorder (ClinVar ID: VCV000555444 / PMID: 27338287). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 27338287). A different missense change at the same codon (p.Gly319Ser) has been reported to be associated with SMPD1-related disorder (ClinVar ID: VCV000992693). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.

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

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine