ClinVar Miner

Submissions for variant NM_007254.4(PNKP):c.1430T>C (p.Met477Thr)

gnomAD frequency: 0.00001  dbSNP: rs766655539
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000685510 SCV000812993 uncertain significance Developmental and epileptic encephalopathy, 12 2022-10-24 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with PNKP-related conditions. This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 477 of the PNKP protein (p.Met477Thr). This variant is present in population databases (rs766655539, gnomAD 0.004%). ClinVar contains an entry for this variant (Variation ID: 565845). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PNKP 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.
Eurofins Ntd Llc (ga) RCV000732653 SCV000860629 uncertain significance not provided 2018-04-12 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000765460 SCV000896751 uncertain significance Microcephaly, seizures, and developmental delay; Ataxia - oculomotor apraxia type 4 2018-10-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV002544715 SCV003661977 uncertain significance Inborn genetic diseases 2022-11-18 criteria provided, single submitter clinical testing The c.1430T>C (p.M477T) alteration is located in exon 16 (coding exon 15) of the PNKP gene. This alteration results from a T to C substitution at nucleotide position 1430, causing the methionine (M) at amino acid position 477 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV000732653 SCV003915288 uncertain significance not provided 2022-10-04 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 22508754)
Mayo Clinic Laboratories, Mayo Clinic RCV000732653 SCV005408884 uncertain significance not provided 2024-04-15 criteria provided, single submitter clinical testing BP4, PM2_moderate

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