U.S. flag

An official website of the United States government

NM_033109.5(PNPT1):c.1592C>G (p.Thr531Arg) AND not provided

Germline classification:
Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:
May 20, 2023
Review status:
criteria provided, conflicting classifications
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001705075.17

Allele description [Variation Report for NM_033109.5(PNPT1):c.1592C>G (p.Thr531Arg)]

NM_033109.5(PNPT1):c.1592C>G (p.Thr531Arg)

Gene:
PNPT1:polyribonucleotide nucleotidyltransferase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p16.1
Genomic location:
Preferred name:
NM_033109.5(PNPT1):c.1592C>G (p.Thr531Arg)
HGVS:
  • NC_000002.12:g.55647357G>C
  • NG_033012.1:g.51554C>G
  • NM_033109.3:c.1592C>G
  • NM_033109.5:c.1592C>GMANE SELECT
  • NP_149100.2:p.Thr531Arg
  • NC_000002.11:g.55874492G>C
  • NM_033109.4:c.1592C>G
  • NM_033109.5:c.1592C>G
Protein change:
T531R
Links:
dbSNP: rs374698153
NCBI 1000 Genomes Browser:
rs374698153
Molecular consequence:
  • NM_033109.5:c.1592C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000491104GeneDx
criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)
Uncertain significance
(Apr 21, 2023)
germlineclinical testing

Citation Link,

SCV002229531Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(May 20, 2023)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV003809127Revvity Omics, Revvity
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significance
(Feb 5, 2021)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

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

Citations

PubMed

Clinical Spectrum and Functional Consequences Associated with Bi-Allelic Pathogenic PNPT1 Variants.

Rius R, Van Bergen NJ, Compton AG, Riley LG, Kava MP, Balasubramaniam S, Amor DJ, Fanjul-Fernandez M, Cowley MJ, Fahey MC, Koenig MK, Enns GM, Sadedin S, Wilson MJ, Tan TY, Thorburn DR, Christodoulou J.

J Clin Med. 2019 Nov 19;8(11). doi:pii: E2020. 10.3390/jcm8112020.

PubMed [citation]
PMID:
31752325
PMCID:
PMC6912252

Heterogeneity of PNPT1 neuroimaging: mitochondriopathy, interferonopathy or both?

Pennisi A, Rötig A, Roux CJ, Lévy R, Henneke M, Gärtner J, Teke Kisa P, Sarioglu FC, Yiş U, Konczal LL, Burkardt DD, Wu S, Gaignard P, Besmond C, Hubert L, Rio M, Barcia G, Munnich A, Boddaert N, Schiff M.

J Med Genet. 2022 Feb;59(2):204-208. doi: 10.1136/jmedgenet-2020-107367. Epub 2020 Nov 16.

PubMed [citation]
PMID:
33199448
See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV000491104.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Observed in the heterozygous state in a patient with global developmental delay, intellectual disability, feeding difficulties, irritability, microcephaly, and dystonia who also harbored a second PNPT1 gene variant; the phase of the variants is unknown (Rius et al., 2019); Observed in trans with variant of uncertain significance in the PNPT1 gene in an individual with encephalopathy, developmental delay, and hearing loss (Pennisi A et al., 2020); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 31752325, 33199448, 36147510, 34740920)

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV002229531.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This variant is present in population databases (rs374698153, gnomAD 0.004%). This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 531 of the PNPT1 protein (p.Thr531Arg). This missense change has been observed in individuals with combined oxidative phosphorylation deficiency (PMID: 31752325, 33199448; external communication). For these reasons, this variant has been classified as Pathogenic. 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 expected to disrupt PNPT1 protein function. ClinVar contains an entry for this variant (Variation ID: 209184).

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

From Revvity Omics, Revvity, SCV003809127.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 15, 2024