ClinVar Miner

Submissions for variant NM_007254.4(PNKP):c.275C>T (p.Thr92Ile)

gnomAD frequency: 0.00010  dbSNP: rs780440711
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000801860 SCV000941658 uncertain significance Developmental and epileptic encephalopathy, 12 2021-11-08 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 92 of the PNKP protein (p.Thr92Ile). This variant is present in population databases (rs780440711, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with PNKP-related conditions. ClinVar contains an entry for this variant (Variation ID: 206383). 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 RCV002514029 SCV003567980 uncertain significance Inborn genetic diseases 2021-07-28 criteria provided, single submitter clinical testing The c.275C>T (p.T92I) alteration is located in exon 4 (coding exon 3) of the PNKP gene. This alteration results from a C to T substitution at nucleotide position 275, causing the threonine (T) at amino acid position 92 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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