NM_001303.4(COX10):c.1007A>T (p.Asp336Val) AND Mitochondrial complex 4 deficiency, nuclear type 3

This record was updated by the submitter. Please see the current version.

Germline classification:: Likely pathogenic (3 submissions)
Last evaluated:: Jul 30, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000007960.8

Allele description

NM_001303.4(COX10):c.1007A>T (p.Asp336Val)

Gene:

COX10:cytochrome c oxidase assembly factor heme A:farnesyltransferase COX10 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p12

Genomic location:

Preferred name:

NM_001303.4(COX10):c.1007A>T (p.Asp336Val)

HGVS:

NC_000017.11:g.14206888A>T
NG_008034.1:g.142487A>T
NM_001303.4:c.1007A>TMANE SELECT
NP_001294.2:p.Asp336Val
NC_000017.10:g.14110205A>T
NM_001303.3:c.1007A>T
Q12887:p.Asp336Val

Protein change:

D336V; ASP336VAL

Links:

UniProtKB: Q12887#VAR_026566; OMIM: 602125.0004; dbSNP: rs104894557

NCBI 1000 Genomes Browser:

rs104894557

Molecular consequence:

NM_001303.4:c.1007A>T - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

loss_of_function_variant [Sequence Ontology: SO:0002054] - Comment(s)

Condition(s)

Name:: Mitochondrial complex 4 deficiency, nuclear type 3
Synonyms:: MITOCHONDRIAL COMPLEX IV DEFICIENCY, NUCLEAR TYPE 3
Identifiers:: MONDO: MONDO:0033635; MedGen: C5436682; OMIM: 619046

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Homologene neighbors for GEO Profiles (Select 44329056) (0)
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Chromosome neighbors for GEO Profiles (Select 44332451) (20)
GEO Profiles
Chromosome neighbors for GEO Profiles (Select 44329228) (20)
GEO Profiles
Chromosome neighbors for GEO Profiles (Select 44333252) (20)
GEO Profiles
KANK3 KN motif and ankyrin repeat domains 3 [Homo sapiens]
KANK3 KN motif and ankyrin repeat domains 3 [Homo sapiens]
Gene ID:256949

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000028165	OMIM	no assertion criteria provided	Pathogenic (Oct 15, 2003)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV002023377	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (May 27, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002776313	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jul 30, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000028165

OMIM

no assertion criteria provided

Pathogenic
(Oct 15, 2003)

germline

literature only

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

SCV002023377

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(May 27, 2021)

germline

clinical testing

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

SCV002776313

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jul 30, 2021)

unknown

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in COX10 result in a defect in mitochondrial heme A biosynthesis and account for multiple, early-onset clinical phenotypes associated with isolated COX deficiency.

Antonicka H, Leary SC, Guercin GH, Agar JN, Horvath R, Kennaway NG, Harding CO, Jaksch M, Shoubridge EA.

Hum Mol Genet. 2003 Oct 15;12(20):2693-702. Epub 2003 Aug 19.

PubMed [citation]

PMID:: 12928484

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, SCV000028165.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a patient with cytochrome c oxidase deficiency (MC4DN3; 619046), Antonicka et al. (2003) identified compound heterozygosity for 2 mutations in exon 7 of the COX10 gene: a 1211A-T transversion and a 1211A-G transition, resulting in an asp336-to-val (D336V) substitution and an asp336-to-gly substitution (D336G; 602125.0005), respectively. The patient presented at 6 weeks of age with hypotrophy, anemia, hypotonia, and lactic acidosis. Brain imaging showed symmetric basal ganglia lesions consistent with Leigh syndrome (see 256000). Skeletal muscle and fibroblast COX activity were 16% and 18% of normal controls, respectively. Codon 336 is predicted to be important to the structure of hydrophilic loop VI/VII, which may be involved in the stabilization of heme B prior to its farnesylation.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV002023377.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Fulgent Genetics, Fulgent Genetics, SCV002776313.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 1, 2024

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