ClinVar Miner

Submissions for variant NM_020964.3(EPG5):c.4367A>G (p.Tyr1456Cys)

gnomAD frequency: 0.00002  dbSNP: rs761064074
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV001027783 SCV001190390 uncertain significance Vici syndrome 2021-03-30 criteria provided, single submitter clinical testing EPG5 NM_020964.2 exon 25 p.Tyr1456Cys (c.4367A>G): This variant has not been reported in the literature but is present in 0.04% (14/34546) of Latino alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/18-43484045-T-C). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. Therefore, the clinical significance of this variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV001027783 SCV002128163 uncertain significance Vici syndrome 2022-06-25 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 1456 of the EPG5 protein (p.Tyr1456Cys). This variant is present in population databases (rs761064074, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with EPG5-related conditions. ClinVar contains an entry for this variant (Variation ID: 827978). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 RCV002552428 SCV003536645 uncertain significance Inborn genetic diseases 2022-08-01 criteria provided, single submitter clinical testing The c.4367A>G (p.Y1456C) alteration is located in exon 25 (coding exon 25) of the EPG5 gene. This alteration results from a A to G substitution at nucleotide position 4367, causing the tyrosine (Y) at amino acid position 1456 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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