NM_000543.5(SMPD1):c.106_107delinsCGCTGGC (p.Val36fs) AND Sphingomyelin/cholesterol lipidosis

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Apr 11, 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:: RCV003230928.1

Allele description [Variation Report for NM_000543.5(SMPD1):c.106_107delinsCGCTGGC (p.Val36fs)]

NM_000543.5(SMPD1):c.106_107delinsCGCTGGC (p.Val36fs)

Gene:

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

Variant type:

Indel

Cytogenetic location:

11p15.4

Genomic location:

Preferred name:

NM_000543.5(SMPD1):c.106_107delinsCGCTGGC (p.Val36fs)

HGVS:

NC_000011.10:g.6390704_6390705delinsCGCTGGC
NG_011780.1:g.5280_5281delinsCGCTGGC
NM_000543.4:c.106_107delinsCGCTGGC
NM_000543.5:c.106_107delinsCGCTGGCMANE SELECT
NM_001007593.3:c.106_107delinsCGCTGGC
NM_001318087.2:c.106_107delinsCGCTGGC
NM_001318088.2:c.-856_-855delinsCGCTGGC
NM_001365135.2:c.106_107delinsCGCTGGC
NP_000534.3:p.Val36fs
NP_001007594.2:p.Val36fs
NP_001305016.1:p.Val36fs
NP_001352064.1:p.Val36fs
NC_000011.9:g.6411934_6411935delinsCGCTGGC
NR_027400.3:n.231_232delinsCGCTGGC
NR_134502.2:n.231_232delinsCGCTGGC

Protein change:

V36fs

Molecular consequence:

NM_001318088.2:c.-856_-855delinsCGCTGGC - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000543.5:c.106_107delinsCGCTGGC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001007593.3:c.106_107delinsCGCTGGC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001318087.2:c.106_107delinsCGCTGGC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001365135.2:c.106_107delinsCGCTGGC - frameshift variant - [Sequence Ontology: SO:0001589]
NR_027400.3:n.231_232delinsCGCTGGC - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_134502.2:n.231_232delinsCGCTGGC - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Sphingomyelin/cholesterol lipidosis
Synonyms:: Niemann-Pick disease
Identifiers:: MONDO: MONDO:0001982; MedGen: C0028064

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003929057	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Apr 11, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003929057

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Apr 11, 2023)

germline

clinical testing

Citation Link

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

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003929057.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Variant summary: SMPD1 c.106_107delinsCGCTGGC (p.Val36ArgfsX43) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 234736 control chromosomes (gnomAD). To our knowledge, no occurrence of c.106_107delinsCGCTGGC in individuals affected with Niemann-Pick Disease and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely 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: Apr 6, 2024

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