ClinVar Miner

Submissions for variant NM_002778.4(PSAP):c.1A>T (p.Met1Leu)

dbSNP: rs121918106
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001857349 SCV002234647 pathogenic Sphingolipid activator protein 1 deficiency 2023-09-21 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of the initiator codon alters PSAP gene expression (PMID: 20484222). ClinVar contains an entry for this variant (Variation ID: 13365). This variant is also known as M1L. Disruption of the initiator codon has been observed in individuals with PSAP-related conditions (PMID: 1371116, 17616409, 20484222). This variant is present in population databases (rs121918106, gnomAD 0.004%). This sequence change affects the initiator methionine of the PSAP mRNA. The next in-frame methionine is located at codon 76.
Molecular Genetics, Royal Melbourne Hospital RCV000014294 SCV004812695 pathogenic Gaucher disease due to saposin C deficiency 2022-04-01 criteria provided, single submitter clinical testing This sequence change in PSAP may cause a truncated or absent protein by altering the start codon of the coding sequence and is predicted to lead to the omission of a critical region of the protein (PMID: 17616409, 17919309; ClinVar: SCV001231459.2, SCV001590882.1). The highest population minor allele frequency in gnomAD v2.1 is 0.004% (3/74,284 alleles) in the European (non-Finnish) population. This variant has been detected in at least five individuals with PSAP-related disorders with prosaposin deficiency from three unrelated families. Of those individuals, three individuals were homozygous and two siblings were compound heterozygous for the variant and a variant of uncertain significance, confirmed in trans (PMID: 1371116, 15944902, 17919309). Patients with this variant have displayed saposin C deficiency or combined saposin deficiency in fibroblasts/cell extracts (PMID: 1371116, 20484222). Based on the classification scheme RMH Modified ACMG Guidelines v1.5.1, this variant is classified as PATHOGENIC. Following criteria are met: PVS1_Strong, PM3, PP1_Moderate, PM2_Supporting, PP4.
OMIM RCV000014293 SCV000034542 pathogenic Combined PSAP deficiency 2007-12-01 no assertion criteria provided literature only
OMIM RCV000014294 SCV000034543 pathogenic Gaucher disease due to saposin C deficiency 2007-12-01 no assertion criteria provided literature only

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