ClinVar Miner

Submissions for variant NM_014855.3(AP5Z1):c.1771T>C (p.Tyr591His)

gnomAD frequency: 0.00006  dbSNP: rs1490632344
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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 RCV000687766 SCV000815352 uncertain significance Hereditary spastic paraplegia 48 2022-07-19 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 567625). This variant has not been reported in the literature in individuals affected with AP5Z1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.04%). This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 591 of the AP5Z1 protein (p.Tyr591His).
GeneDx RCV004820090 SCV005440972 uncertain significance not provided 2024-06-25 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV004957994 SCV005454104 uncertain significance Inborn genetic diseases 2024-08-06 criteria provided, single submitter clinical testing The c.1771T>C (p.Y591H) alteration is located in exon 14 (coding exon 14) of the AP5Z1 gene. This alteration results from a T to C substitution at nucleotide position 1771, causing the tyrosine (Y) at amino acid position 591 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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