Submissions for variant NM_014855.3(AP5Z1):c.1168C>G (p.Gln390Glu)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003067142	SCV003453250	uncertain significance	Hereditary spastic paraplegia 48	2024-02-23	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 390 of the AP5Z1 protein (p.Gln390Glu). This variant is present in population databases (rs377565484, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with AP5Z1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2146462). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt AP5Z1 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV003269415	SCV003979243	uncertain significance	Inborn genetic diseases	2023-05-17	criteria provided, single submitter	clinical testing	The c.1168C>G (p.Q390E) alteration is located in exon 10 (coding exon 10) of the AP5Z1 gene. This alteration results from a C to G substitution at nucleotide position 1168, causing the glutamine (Q) at amino acid position 390 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.