ClinVar Miner

Submissions for variant NM_000543.5(SMPD1):c.83C>T (p.Pro28Leu) (rs556155962)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000728133 SCV000855667 likely benign not specified 2017-07-10 criteria provided, single submitter clinical testing
Invitae RCV000915596 SCV001060811 benign Niemann-Pick disease, type B; Niemann-Pick disease, type A 2020-11-11 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001107111 SCV001264242 uncertain significance Niemann-Pick disease, type A 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001357849 SCV001553438 uncertain significance not provided no assertion criteria provided clinical testing The SMPD1 p.Pro28Leu variant was not identified in the literature but was identified in dbSNP (ID: rs556155962) and ClinVar (classified as likely benign by EGL Genetics). The variant was identified in control databases in 143 of 275324 chromosomes (2 homozygous) at a frequency of 0.0005194 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: South Asian in 140 of 30476 chromosomes (freq: 0.004594), Other in 1 of 7038 chromosomes (freq: 0.000142), African in 1 of 23448 chromosomes (freq: 0.000043) and Latino in 1 of 35150 chromosomes (freq: 0.000028), but was not observed in the Ashkenazi Jewish, East Asian, European (Finnish), or European (non-Finnish) populations. The p.Pro28 residue is conserved in mammals but not in more distantly related organisms however four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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