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NM_007254.4(PNKP):c.1549C>T (p.Gln517Ter) AND Inborn genetic diseases

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Mar 31, 2020
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:

Allele description [Variation Report for NM_007254.4(PNKP):c.1549C>T (p.Gln517Ter)]

NM_007254.4(PNKP):c.1549C>T (p.Gln517Ter)

PNKP:polynucleotide kinase 3'-phosphatase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_007254.4(PNKP):c.1549C>T (p.Gln517Ter)
  • NC_000019.10:g.49861265G>A
  • NG_027717.1:g.11301C>T
  • NG_050666.1:g.17422G>A
  • NM_007254.4:c.1549C>TMANE SELECT
  • NP_009185.2:p.Gln517Ter
  • NC_000019.9:g.50364522G>A
  • NM_007254.2:c.1549C>T
  • NM_007254.3:c.1549C>T
Protein change:
Q517*; GLN517TER
OMIM: 605610.0009; dbSNP: rs774995635
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_007254.4:c.1549C>T - nonsense - [Sequence Ontology: SO:0001587]


Inborn genetic diseases
MeSH: D030342; MedGen: C0950123

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV002709411Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)
Uncertain significance
(Mar 31, 2020)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing



The molecular architecture of the mammalian DNA repair enzyme, polynucleotide kinase.

Bernstein NK, Williams RS, Rakovszky ML, Cui D, Green R, Karimi-Busheri F, Mani RS, Galicia S, Koch CA, Cass CE, Durocher D, Weinfeld M, Glover JN.

Mol Cell. 2005 Mar 4;17(5):657-70.

PubMed [citation]

The polynucleotide kinase 3'-phosphatase gene (PNKP) is involved in Charcot-Marie-Tooth disease (CMT2B2) previously related to MED25.

Leal A, Bogantes-Ledezma S, Ekici AB, Uebe S, Thiel CT, Sticht H, Berghoff M, Berghoff C, Morera B, Meisterernst M, Reis A.

Neurogenetics. 2018 Dec;19(4):215-225. doi: 10.1007/s10048-018-0555-7. Epub 2018 Jul 24.

PubMed [citation]

Details of each submission

From Ambry Genetics, SCV002709411.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)


The p.Q517* variant (also known as c.1549C>T), located in coding exon 16 of the PNKP gene, results from a C to T substitution at nucleotide position 1549. This changes the amino acid from a glutamine to a stop codon within coding exon 16. In a large Costa Rican family, this variant was homozygous in individuals with Charcot-Marie-Tooth (CMT) disease with axonal neuropathy and autosomal recessive pattern of inheritance; all the affected individuals were also homozygous for the p.A335V MED25 variant (Leal A et al. Neurogenetics, 2018 12;19:215-225). In five other Costa Rican families with CMT, this variant was compound heterozygous with another PNKP nonsense variant in affected individuals; these individuals were also heterozygous for the p.A335V MED25 variant, suggesting a common ancestral haploytpe. Premature stop codons are typically deleterious in nature; however, this stop codon occurs at the 3' terminus of PNKP, is not expected to trigger nonsense-mediated mRNA decay, and impacts only the last 5 amino acids of the protein. The exact functional impact of these removed amino acids is unknown at this time. Based on available evidence to date, the clinical significance of this alteration remains unclear.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 1, 2024