NM_000543.5(SMPD1):c.1103del (p.Phe368fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 27, 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:: RCV003779123.2

Allele description [Variation Report for NM_000543.5(SMPD1):c.1103del (p.Phe368fs)]

NM_000543.5(SMPD1):c.1103del (p.Phe368fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

11p15.4

Genomic location:

Preferred name:

NM_000543.5(SMPD1):c.1103del (p.Phe368fs)

HGVS:

NC_000011.10:g.6393227del
NG_011780.1:g.7803del
NG_029615.1:g.31189del
NM_000543.5:c.1103delMANE SELECT
NM_001007593.3:c.1100del
NM_001318087.2:c.1103del
NM_001318088.2:c.182del
NM_001365135.2:c.1132-390del
NP_000534.3:p.Phe368fs
NP_001007594.2:p.Phe367fs
NP_001305016.1:p.Phe368fs
NP_001305017.1:p.Phe61fs
NC_000011.9:g.6414456del
NC_000011.9:g.6414457del
NR_134502.2:n.575del

Protein change:

F367fs

Molecular consequence:

NM_000543.5:c.1103del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001007593.3:c.1100del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001318087.2:c.1103del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001318088.2:c.182del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001365135.2:c.1132-390del - intron variant - [Sequence Ontology: SO:0001627]
NR_134502.2:n.575del - 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
SCV004594593	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 27, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 32778503, 33675270, 12369017, 15221801, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004594593

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 27, 2023)

germline

clinical testing

PubMed (5)
[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

[A novel mutation in two spanish children with the Niemann Pick disease: Description of genotype, acid sphingomyelinase activity, phenotype and review].

Del Villar-Guerra P, Reig C, Irún P, Moreno B, Giraldo P, Cebolla JJ.

An Pediatr (Engl Ed). 2021 May;94(5):327-330. doi: 10.1016/j.anpedi.2020.03.021. Epub 2020 Aug 8. Spanish. No abstract available.

PubMed [citation]

PMID:: 32778503

Clinical, biochemical, and genotype-phenotype correlations of 118 patients with Niemann-Pick disease Types A/B.

Hu J, Maegawa GHB, Zhan X, Gao X, Wang Y, Xu F, Qiu W, Han L, Gu X, Zhang H.

Hum Mutat. 2021 May;42(5):614-625. doi: 10.1002/humu.24192. Epub 2021 Mar 19.

PubMed [citation]

PMID:: 33675270

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004594593.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This premature translational stop signal has been observed in individual(s) with Niemann-Pick disease (PMID: 32778503, 33675270). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Phe368Serfs*17) 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). 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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