NM_000543.5(SMPD1):c.107_112del (p.Val36_Leu37del) AND not specified

Germline classification:: Benign (1 submission)
Last evaluated:: Mar 8, 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:: RCV000252024.7

Allele description [Variation Report for NM_000543.5(SMPD1):c.107_112del (p.Val36_Leu37del)]

NM_000543.5(SMPD1):c.107_112del (p.Val36_Leu37del)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

11p15.4

Genomic location:

Preferred name:

NM_000543.5(SMPD1):c.107_112del (p.Val36_Leu37del)

HGVS:

NC_000011.10:g.6390705_6390710del
NG_011780.1:g.5281_5286del
NM_000543.5:c.107_112delMANE SELECT
NM_001007593.3:c.107_112del
NM_001318087.2:c.107_112del
NM_001318088.2:c.-855_-850del
NM_001365135.2:c.107_112del
NP_000534.3:p.Val36_Leu37del
NP_001007594.2:p.Val36_Leu37del
NP_001305016.1:p.Val36_Leu37del
NP_001352064.1:p.Val36_Leu37del
NC_000011.9:g.6411931_6411936del
NC_000011.9:g.6411935_6411940del
NM_000543.4:c.107_112del
NM_000543.4:c.107_112del6
NM_000543.4:c.107_112delTGCTGG
NR_027400.3:n.232_237del
NR_134502.2:n.232_237del

Links:

dbSNP: rs775860642

NCBI 1000 Genomes Browser:

rs775860642

Molecular consequence:

NM_001318088.2:c.-855_-850del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000543.5:c.107_112del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001007593.3:c.107_112del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001318087.2:c.107_112del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001365135.2:c.107_112del - inframe_deletion - [Sequence Ontology: SO:0001822]
NR_027400.3:n.232_237del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_134502.2:n.232_237del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002500210	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Mar 8, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002500210

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Benign
(Mar 8, 2022)

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, SCV002500210.1

#	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.107_112delTGCTGG (p.Val36_Leu37del) results in an in-frame deletion that is predicted to remove two amino acids from the encoded protein. The variant allele was found at a frequency of 0.0026 in 232506 control chromosomes, predominantly at a frequency of 0.0038 within the South Asian subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 1.7 fold of the estimated maximal expected allele frequency for a pathogenic variant in SMPD1 causing Niemann-Pick Disease phenotype (0.0022), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Two classified as benign/likely benign while one classified as VUS. Based on the evidence outlined above, the variant was classified as benign.

#	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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