Submissions for variant NM_002778.4(PSAP):c.623T>G (p.Ile208Ser)

gnomAD frequency: 0.00008  dbSNP: rs200319381

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000514444	SCV000610142	uncertain significance	not provided	2017-03-09	criteria provided, single submitter	clinical testing
GeneDx	RCV000514444	SCV000621587	uncertain significance	not provided	2017-10-10	criteria provided, single submitter	clinical testing	The I208S variant in the PSAP gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The I208S variant is observed in 160/34420 (0.46%) alleles from individuals of Latino background, in the ExAC dataset, an individuals were reported to be homozygous (Lek et al., 2016). The I208S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret I208S as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001081218	SCV001049205	likely benign	Sphingolipid activator protein 1 deficiency	2025-01-19	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001272678	SCV001454917	likely benign	Metachromatic leukodystrophy	2019-11-11	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003962415	SCV004784854	likely benign	PSAP-related disorder	2022-08-05	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).