ClinVar Miner

Submissions for variant NM_006267.5(RANBP2):c.1957A>G (p.Thr653Ala)

gnomAD frequency: 0.00018  dbSNP: rs149578420
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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 RCV000805729 SCV000945697 uncertain significance Familial acute necrotizing encephalopathy 2023-12-18 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 653 of the RANBP2 protein (p.Thr653Ala). This variant is present in population databases (rs149578420, gnomAD 0.03%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with RANBP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 650559). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The alanine 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.
Fulgent Genetics, Fulgent Genetics RCV000805729 SCV002780306 uncertain significance Familial acute necrotizing encephalopathy 2021-08-09 criteria provided, single submitter clinical testing
Breakthrough Genomics, Breakthrough Genomics RCV004693316 SCV005187847 uncertain significance not provided criteria provided, single submitter not provided

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