NM_000543.5(SMPD1):c.901G>A (p.Val301Ile) AND Sphingomyelin/cholesterol lipidosis

Germline classification:: Likely benign (1 submission)
Last evaluated:: Jan 22, 2020
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:: RCV001249056.3

Allele description [Variation Report for NM_000543.5(SMPD1):c.901G>A (p.Val301Ile)]

NM_000543.5(SMPD1):c.901G>A (p.Val301Ile)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.4

Genomic location:

Preferred name:

NM_000543.5(SMPD1):c.901G>A (p.Val301Ile)

HGVS:

NC_000011.10:g.6391966G>A
NG_011780.1:g.6542G>A
NM_000543.4(SMPD1):c.901G>A
NM_000543.5:c.901G>AMANE SELECT
NM_001007593.3:c.898G>A
NM_001318087.2:c.901G>A
NM_001318088.2:c.-61G>A
NM_001365135.2:c.901G>A
NP_000534.3:p.Val301Ile
NP_001007594.2:p.Val300Ile
NP_001305016.1:p.Val301Ile
NP_001352064.1:p.Val301Ile
NC_000011.9:g.6413196G>A
NM_000543.4(SMPD1):c.901G>A
NM_000543.4:c.901G>A
NM_000543.5:c.901G>A
NR_027400.3:n.1026G>A
p.Val301Ile

Protein change:

V300I

Links:

dbSNP: rs2723669

NCBI 1000 Genomes Browser:

rs2723669

Molecular consequence:

NM_001318088.2:c.-61G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000543.5:c.901G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001007593.3:c.898G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001318087.2:c.901G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365135.2:c.901G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_027400.3:n.1026G>A - 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
SCV001423003	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Jan 22, 2020)	germline	curation	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001423003

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Jan 22, 2020)

germline

curation

PubMed (1)
[See all records that cite this PMID]

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	curation

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV001423003.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (1)

Description

The p.Val301Ile variant in SMPD1 (also known as p.Val299Ile due to a difference in cDNA numbering) has not been previously reported in individuals with Niemann-Pick disease, but has been identified in 1.166% (291/24858) of African chromosomes, including 1 homozygote, 0.116% (41/35436) of Latino chromosomes, and 0.0196% (6/30616) of South Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs2723669. This variant has also been reported in ClinVar (VariationID: 305201) as a VUS by Illumina Clinical Services Laboratory, as likely benign by Mayo Clinic Genetic Testing Laboratories, and as Benign by EGL Genetic Diagnostics. Computational prediction tools, including splice predictors, and conservation analyses suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely benign. ACMG/AMP Criteria applied: BS1, BP4 (Richards 2015).

#	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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