ClinVar Miner

Submissions for variant NM_014855.3(AP5Z1):c.1795G>A (p.Gly599Ser)

gnomAD frequency: 0.00009  dbSNP: rs369917291
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001237634 SCV001410401 uncertain significance Hereditary spastic paraplegia 48 2021-10-14 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 599 of the AP5Z1 protein (p.Gly599Ser). The glycine residue is weakly conserved and there is a small physicochemical difference between glycine and serine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with AP5Z1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001847202 SCV002106160 uncertain significance Hereditary spastic paraplegia 2020-08-11 criteria provided, single submitter clinical testing
Ambry Genetics RCV002563896 SCV003696436 uncertain significance Inborn genetic diseases 2022-01-10 criteria provided, single submitter clinical testing The c.1795G>A (p.G599S) alteration is located in exon 14 (coding exon 14) of the AP5Z1 gene. This alteration results from a G to A substitution at nucleotide position 1795, causing the glycine (G) at amino acid position 599 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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