NM_000543.5(SMPD1):c.110_116del (p.Leu37fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 15, 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:: RCV001232656.6

Allele description [Variation Report for NM_000543.5(SMPD1):c.110_116del (p.Leu37fs)]

NM_000543.5(SMPD1):c.110_116del (p.Leu37fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

11p15.4

Genomic location:

Preferred name:

NM_000543.5(SMPD1):c.110_116del (p.Leu37fs)

HGVS:

NC_000011.10:g.6390708_6390714del
NG_011780.1:g.5284_5290del
NM_000543.5:c.110_116delMANE SELECT
NM_001007593.3:c.110_116del
NM_001318087.2:c.110_116del
NM_001318088.2:c.-852_-846del
NM_001365135.2:c.110_116del
NP_000534.3:p.Leu37fs
NP_001007594.2:p.Leu37fs
NP_001305016.1:p.Leu37fs
NP_001352064.1:p.Leu37fs
NC_000011.9:g.6411938_6411944del
NM_000543.4:c.110_116del
NR_027400.3:n.235_241del
NR_134502.2:n.235_241del

Protein change:

L37fs

Links:

dbSNP: rs1847863441

NCBI 1000 Genomes Browser:

rs1847863441

Molecular consequence:

NM_001318088.2:c.-852_-846del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000543.5:c.110_116del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001007593.3:c.110_116del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001318087.2:c.110_116del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001365135.2:c.110_116del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_027400.3:n.235_241del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_134502.2:n.235_241del - 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
SCV001405221	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 15, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 12369017, 15221801, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001405221

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 15, 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

The demographics and distribution of type B Niemann-Pick disease: novel mutations lead to new genotype/phenotype correlations.

Simonaro CM, Desnick RJ, McGovern MM, Wasserstein MP, Schuchman EH.

Am J Hum Genet. 2002 Dec;71(6):1413-9. Epub 2002 Oct 4.

PubMed [citation]

PMID:: 12369017
PMCID:: PMC378582

Screening of 25 Italian patients with Niemann-Pick A reveals fourteen new mutations, one common and thirteen private, in SMPD1.

Ricci V, Stroppiano M, Corsolini F, Di Rocco M, Parenti G, Regis S, Grossi S, Biancheri R, Mazzotti R, Filocamo M.

Hum Mutat. 2004 Jul;24(1):105.

PubMed [citation]

PMID:: 15221801

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001405221.5

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

Description

This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SMPD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 959328). For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Leu37Argfs*38) in the SMPD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SMPD1 are known to be pathogenic (PMID: 12369017, 15221801).

#	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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