Submissions for variant NM_033419.5(PGAP3):c.320C>T (p.Ser107Leu)

gnomAD frequency: 0.00017  dbSNP: rs202146344

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001380577	SCV000576501	pathogenic	not provided	2024-09-20	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27120253, 28327575, 29531774, 29310717, 30345601, 37010288)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001380577	SCV001578689	pathogenic	not provided	2024-10-16	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 107 of the PGAP3 protein (p.Ser107Leu). This variant is present in population databases (rs202146344, gnomAD 0.03%). This missense change has been observed in individual(s) with PGAP3-congenital disorder of glycosylation (PMID: 27120253, 28327575, 30345601). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 224643). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt PGAP3 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity	RCV000210258	SCV003809233	likely pathogenic	Hyperphosphatasia with intellectual disability syndrome 4	2022-04-07	criteria provided, single submitter	clinical testing
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV000210258	SCV004807363	likely pathogenic	Hyperphosphatasia with intellectual disability syndrome 4	2024-10-07	criteria provided, single submitter	clinical testing
Institute for Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin	RCV000210258	SCV000266257	pathogenic	Hyperphosphatasia with intellectual disability syndrome 4	2016-03-01	no assertion criteria provided	research	Disease causing variant in homozygous or compound heterozygous state