ClinVar Miner

Submissions for variant NM_006267.5(RANBP2):c.2997A>G (p.Ile999Met)

gnomAD frequency: 0.00013  dbSNP: rs201152981
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000547943 SCV000646793 uncertain significance Familial acute necrotizing encephalopathy 2022-09-26 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 output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 469444). This variant has not been reported in the literature in individuals affected with RANBP2-related conditions. This variant is present in population databases (rs201152981, gnomAD 0.03%). This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 999 of the RANBP2 protein (p.Ile999Met).
Ambry Genetics RCV004024084 SCV003868657 uncertain significance not specified 2023-01-06 criteria provided, single submitter clinical testing The c.2997A>G (p.I999M) alteration is located in exon 20 (coding exon 20) of the RANBP2 gene. This alteration results from a A to G substitution at nucleotide position 2997, causing the isoleucine (I) at amino acid position 999 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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