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NM_001164811.2(PET117):c.172C>T (p.Gln58Ter) AND Mitochondrial complex 4 deficiency, nuclear type 19

Germline classification:
Likely pathogenic (2 submissions)
Last evaluated:
Dec 4, 2020
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV001260985.2

Allele description [Variation Report for NM_001164811.2(PET117):c.172C>T (p.Gln58Ter)]

NM_001164811.2(PET117):c.172C>T (p.Gln58Ter)

Genes:
PET117:PET117 cytochrome c oxidase chaperone [Gene - OMIM - HGNC]
KAT14:lysine acetyltransferase 14 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
20p11.23
Genomic location:
Preferred name:
NM_001164811.2(PET117):c.172C>T (p.Gln58Ter)
HGVS:
  • NC_000020.11:g.18142283C>T
  • NM_001164811.2:c.172C>TMANE SELECT
  • NM_001384192.3:c.-378C>T
  • NM_001392069.1:c.-378C>T
  • NM_001392070.1:c.-378C>T
  • NM_001392071.1:c.-378C>T
  • NM_001392072.1:c.-378C>T
  • NM_001392073.1:c.-378C>TMANE SELECT
  • NM_001392074.1:c.-378C>T
  • NM_001392075.1:c.-378C>T
  • NM_001392076.1:c.-378C>T
  • NM_001392077.1:c.-378C>T
  • NM_001392078.1:c.-378C>T
  • NM_001392079.1:c.-378C>T
  • NM_001392080.1:c.-378C>T
  • NM_001392081.1:c.-378C>T
  • NM_020536.7:c.-378C>T
  • NP_001158283.1:p.Gln58Ter
  • NC_000020.10:g.18122927C>T
Nucleotide change:
172C-T
Protein change:
Q58*
Links:
OMIM: 614771.0001; dbSNP: rs2037617604
NCBI 1000 Genomes Browser:
rs2037617604
Molecular consequence:
  • NM_001384192.3:c.-378C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001392069.1:c.-378C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001392070.1:c.-378C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001392071.1:c.-378C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001392072.1:c.-378C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001392073.1:c.-378C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001392074.1:c.-378C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001392075.1:c.-378C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001392076.1:c.-378C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001392077.1:c.-378C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001392078.1:c.-378C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001392079.1:c.-378C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001392080.1:c.-378C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001392081.1:c.-378C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_020536.7:c.-378C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001164811.2:c.172C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Mitochondrial complex 4 deficiency, nuclear type 19
Synonyms:
MITOCHONDRIAL COMPLEX IV DEFICIENCY, NUCLEAR TYPE 19
Identifiers:
MONDO: MONDO:0033654; MedGen: C5436723; OMIM: 619063

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001438359OMIM
no assertion criteria provided
Pathogenic
(Oct 23, 2020) 		germlineliterature only

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

SCV001468548SIB Swiss Institute of Bioinformatics
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Dec 4, 2020) 		unknowncuration

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providedunknownunknownnot providednot providednot providednot providednot providedcuration

Citations

PubMed

Mutated PET117 causes complex IV deficiency and is associated with neurodevelopmental regression and medulla oblongata lesions.

Renkema GH, Visser G, Baertling F, Wintjes LT, Wolters VM, van Montfrans J, de Kort GAP, Nikkels PGJ, van Hasselt PM, van der Crabben SN, Rodenburg RJT.

Hum Genet. 2017 Jun;136(6):759-769. doi: 10.1007/s00439-017-1794-7. Epub 2017 Apr 6.

PubMed [citation]
PMID:
28386624
PMCID:
PMC5429353

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From OMIM, SCV001438359.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In 2 sisters, born of consanguineous Moroccan parents, with mitochondrial complex IV deficiency nuclear type 19 (MC4DN19; 619063), Renkema et al. (2017) identified a homozygous c.172C-T transition (c.172C-T, NM_001164811) in the PET117 gene, resulting in a premature stop codon at position 58 of the protein. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not found in the dbSNP, Exome Variant Server, or ExAC databases, or in an in-house database. Patient cells showed decreased complex IV activity and protein levels, which could be restored by transfection of wildtype PET117 cDNA. Analysis of PET117 protein levels in patient cells could not be performed. In early childhood, the patients had developmental delay and regression, manifest as loss of motor skills, impaired intellectual development, and speech decline. Brain imaging showed T2-weighted lesions in the medulla oblongata.

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

From SIB Swiss Institute of Bioinformatics, SCV001468548.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (2)

Description

This variant is interpreted as Likely pathogenic for Mitochondrial complex IV deficiency,nuclear type 19, autosomal recessive. The following ACMG Tag(s) were applied: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (PM2); Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PP1); Protein length changes as a result of in-frame deletions/insertions in a nonrepeat region or stop-loss variants (PM4); Well-established functional studies show a deleterious effect (PS3 downgraded to moderate).

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

Last Updated: Apr 23, 2022