ClinVar Miner

Submissions for variant NM_005765.3(ATP6AP2):c.490G>A (p.Val164Ile) (rs142013283)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000186814 SCV000240384 likely benign not specified 2016-12-29 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000640918 SCV000762522 uncertain significance Mental retardation, X-linked, syndromic, Hedera type 2019-12-24 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 164 of the ATP6AP2 protein (p.Val164Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs142013283, ExAC 0.02%). This variant has not been reported in the literature in individuals with ATP6AP2-related disease. ClinVar contains an entry for this variant (Variation ID: 204912). 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 isoleucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000767901 SCV000898540 uncertain significance Mental retardation, X-linked, syndromic, Hedera type; Parkinsonism with spasticity, X-linked 2018-10-25 criteria provided, single submitter clinical testing ATP6AP2 NM_005765.2 exon 5 p.Val164Ile (c.490G>A): This variant has not been reported in the literature but is present in 3/27186 Latino alleles, including 1 hemizygote in the Genome Aggregation Database ( This variant is present in ClinVar (Variation ID:204912). This variant amino acid Isoleucine (Ile) is present in >30 species and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

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