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NM_000543.5(SMPD1):c.1427G>A (p.Arg476Gln) AND SMPD1-related disorder

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jul 29, 2024
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV003959931.2

Allele description [Variation Report for NM_000543.5(SMPD1):c.1427G>A (p.Arg476Gln)]

NM_000543.5(SMPD1):c.1427G>A (p.Arg476Gln)

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.1427G>A (p.Arg476Gln)
HGVS:
  • NC_000011.10:g.6393982G>A
  • NG_011780.1:g.8558G>A
  • NG_029615.1:g.30433C>T
  • NM_000543.4(SMPD1):c.1427G>A
  • NM_000543.5:c.1427G>AMANE SELECT
  • NM_001007593.3:c.1424G>A
  • NM_001318087.2:c.1427G>A
  • NM_001318088.2:c.506G>A
  • NM_001365135.2:c.1295G>A
  • NP_000534.3:p.Arg476Gln
  • NP_001007594.2:p.Arg475Gln
  • NP_001305016.1:p.Arg476Gln
  • NP_001305017.1:p.Arg169Gln
  • NP_001352064.1:p.Arg432Gln
  • NC_000011.9:g.6415212G>A
  • NC_000011.9:g.6415212G>A
  • NM_000543.4(SMPD1):c.1427G>A
  • NM_000543.4:c.1427G>A
  • NR_027400.3:n.1380G>A
  • NR_134502.2:n.899G>A
  • p.Arg476Gln
Protein change:
R169Q
Links:
dbSNP: rs763566905
NCBI 1000 Genomes Browser:
rs763566905
Molecular consequence:
  • NM_000543.5:c.1427G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001007593.3:c.1424G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001318087.2:c.1427G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001318088.2:c.506G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365135.2:c.1295G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_027400.3:n.1380G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_134502.2:n.899G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
SMPD1-related disorder
Synonyms:
SMPD1-related condition
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004770272PreventionGenetics, part of Exact Sciences
no assertion criteria provided
Likely pathogenic
(Jul 29, 2024) 		germlineclinical testing

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004770272.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The SMPD1 c.1427G>A variant is predicted to result in the amino acid substitution p.Arg476Gln. This variant, along with a second SMPD1 variant, was reported in an individual with Niemann-Pick disease (Zampieri et al. 2016. PubMed ID: 26499107). This variant has also been reported in an individual with Parkinson's disease (Table S3, Robak et al. 2017. PubMed ID: 29140481). Additionally, different missense variants affecting this amino acid (p.Arg476Gln, p.Arg476Gly) have been reported as pathogenic (Irun et al. 2013. PubMed ID: 23252888; Hu et al. 2021. PubMed ID: 33675270). This variant is reported in 0.016% of alleles in individuals of South Asian descent in gnomAD and in ClinVar this variant has conflicting interpretations of uncertain, likely pathogenic, and pathogenic (https://www.ncbi.nlm.nih.gov/clinvar/variation/385606/). Taken together, this variant is interpreted as likely pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 30, 2024