ClinVar Miner

Submissions for variant NM_000543.5(SMPD1):c.887G>A (p.Arg296Gln) (rs35824453)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000175631 SCV000227155 benign not specified 2015-05-20 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000224205 SCV000280601 benign not provided 2015-08-25 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000383492 SCV000372934 benign Niemann-Pick disease, type A 2018-03-06 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000175631 SCV000920242 likely benign not specified 2018-06-04 criteria provided, single submitter clinical testing Variant summary: SMPD1 c.887G>A (p.Arg296Gln) results in a conservative amino acid change located in the Calcineurin-like ApaH type phosphoesterase domain of the encoded protein sequence. Four of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0044 in 277234 control chromosomes in the gnomAD database, including 27 homozygotes. The observed variant frequency is approximately 1.96 fold of the estimated maximal expected allele frequency for a pathogenic variant in SMPD1 causing Niemann-Pick Disease Type A phenotype (0.0022), strongly suggesting that the variant is benign. c.887G>A has been reported in the literature in individuals affected with Niemann-Pick Disease Type A. These report(s) do not provide unequivocal conclusions about association of the variant with Niemann-Pick Disease Type A. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Invitae RCV001081402 SCV001116891 benign Niemann-Pick disease, type B; Niemann-Pick disease, type A 2020-12-05 criteria provided, single submitter clinical testing
GeneDx RCV000224205 SCV001888861 benign not provided 2020-05-06 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 15221801, 21228398, 20981092)

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