ClinVar Miner

Submissions for variant NM_017951.5(SMPD4):c.1220C>T (p.Pro407Leu)

gnomAD frequency: 0.00004  dbSNP: rs747433356
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
SIB Swiss Institute of Bioinformatics RCV000853217 SCV001245386 uncertain significance Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies 2020-02-14 criteria provided, single submitter curation This variant is interpreted as a variant of uncertain significance for Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies, autosomal recessive. The following ACMG Tag(s) were applied: PM2, PP3, PP1.
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV000853217 SCV001430802 uncertain significance Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies 2020-05-29 criteria provided, single submitter research The homozygous p.Pro446Leu variant in SMPD4 was identified by our study in 1 individual with neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies (PMID: 31495489). The variant has been identified in 0.006% (2/35360) of Latino chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported in ClinVar (Variation ID#: 691972) as pathogenic by OMIM. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2, PM3_supporting (Richards 2015).
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre RCV000853217 SCV004808122 uncertain significance Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies 2024-03-29 criteria provided, single submitter clinical testing
OMIM RCV000853217 SCV000996029 pathogenic Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies 2019-10-16 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.