NM_000543.5(SMPD1):c.1589del (p.Gly530fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 6, 2022
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:: RCV002890334.3

Allele description [Variation Report for NM_000543.5(SMPD1):c.1589del (p.Gly530fs)]

NM_000543.5(SMPD1):c.1589del (p.Gly530fs)

Gene:

SMPD1:sphingomyelin phosphodiesterase 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

11p15.4

Genomic location:

Preferred name:

NM_000543.5(SMPD1):c.1589del (p.Gly530fs)

HGVS:

NC_000011.10:g.6394300del
NG_011780.1:g.8876del
NG_029615.1:g.30117del
NM_000543.5:c.1589delMANE SELECT
NM_001007593.3:c.1586del
NM_001318087.2:c.*82del
NM_001318088.2:c.668del
NM_001365135.2:c.1457del
NP_000534.3:p.Gly530fs
NP_001007594.2:p.Gly529fs
NP_001305017.1:p.Gly223fs
NP_001352064.1:p.Gly486fs
NC_000011.9:g.6415528del
NC_000011.9:g.6415530del
NR_027400.3:n.1542del
NR_134502.2:n.1081del

Protein change:

G223fs

Molecular consequence:

NM_001318087.2:c.*82del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000543.5:c.1589del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001007593.3:c.1586del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001318088.2:c.668del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001365135.2:c.1457del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_027400.3:n.1542del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_134502.2:n.1081del - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003242355	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 6, 2022)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 1885770, 8225311, 12694237, 19405096, 23252888, 24643943, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003242355

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 6, 2022)

germline

clinical testing

PubMed (7)
[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

Niemann-Pick type B disease. Identification of a single codon deletion in the acid sphingomyelinase gene and genotype/phenotype correlations in type A and B patients.

Levran O, Desnick RJ, Schuchman EH.

J Clin Invest. 1991 Sep;88(3):806-10.

PubMed [citation]

PMID:: 1885770
PMCID:: PMC295465

Deletion of arginine (608) in acid sphingomyelinase is the prevalent mutation among Niemann-Pick disease type B patients from northern Africa.

Vanier MT, Ferlinz K, Rousson R, Duthel S, Louisot P, Sandhoff K, Suzuki K.

Hum Genet. 1993 Oct;92(4):325-30.

PubMed [citation]

PMID:: 8225311

See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003242355.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This variant has not been reported in the literature in individuals affected with SMPD1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gly530Glufs*83) in the SMPD1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 102 amino acid(s) of the SMPD1 protein. This variant disrupts a region of the SMPD1 protein in which other variant(s) (p.Arg610del) have been determined to be pathogenic (PMID: 1885770, 8225311, 12694237, 19405096, 23252888, 24643943). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	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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