NM_016138.5(COQ7):c.422T>A (p.Val141Glu) AND Primary coenzyme Q10 deficiency 8

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 1, 2024
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:: RCV000203513.4

Allele description [Variation Report for NM_016138.5(COQ7):c.422T>A (p.Val141Glu)]

NM_016138.5(COQ7):c.422T>A (p.Val141Glu)

Gene:

COQ7:coenzyme Q7, hydroxylase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p12.3

Genomic location:

Preferred name:

NM_016138.5(COQ7):c.422T>A (p.Val141Glu)

HGVS:

NC_000016.10:g.19075775T>A
NG_046596.1:g.13181T>A
NM_001190983.2:c.308T>A
NM_001370489.1:c.380T>A
NM_001370490.1:c.422T>A
NM_001370491.1:c.380T>A
NM_001370492.1:c.308T>A
NM_001370493.1:c.308T>A
NM_001370494.1:c.308T>A
NM_001370495.1:c.308T>A
NM_016138.5:c.422T>AMANE SELECT
NP_001177912.1:p.Val103Glu
NP_001357418.1:p.Val127Glu
NP_001357419.1:p.Val141Glu
NP_001357420.1:p.Val127Glu
NP_001357421.1:p.Val103Glu
NP_001357422.1:p.Val103Glu
NP_001357423.1:p.Val103Glu
NP_001357424.1:p.Val103Glu
NP_057222.2:p.Val141Glu
NC_000016.9:g.19087097T>A
NM_016138.4:c.422T>A
NR_163448.1:n.535T>A
NR_163449.1:n.513T>A
NR_163450.1:n.358T>A
Q99807:p.Val141Glu

Protein change:

V103E; VAL141GLU

Links:

UniProtKB: Q99807#VAR_076370; OMIM: 601683.0001; dbSNP: rs864321686

NCBI 1000 Genomes Browser:

rs864321686

Molecular consequence:

NM_001190983.2:c.308T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370489.1:c.380T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370490.1:c.422T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370491.1:c.380T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370492.1:c.308T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370493.1:c.308T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370494.1:c.308T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370495.1:c.308T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_016138.5:c.422T>A - missense variant - [Sequence Ontology: SO:0001583]
NR_163448.1:n.535T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_163449.1:n.513T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_163450.1:n.358T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Name:: Primary coenzyme Q10 deficiency 8
Identifiers:: MONDO: MONDO:0014754; MedGen: C4225226; OMIM: 616733

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000258602	OMIM	no assertion criteria provided	Pathogenic (Nov 1, 2015)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV004697822	Centre for Inherited Metabolic Diseases, Karolinska University Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 1, 2024)	inherited	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

SCV000258602

OMIM

no assertion criteria provided

Pathogenic
(Nov 1, 2015)

germline

literature only

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

SCV004697822

Centre for Inherited Metabolic Diseases, Karolinska University Hospital

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 1, 2024)

inherited

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	inherited	yes	1	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

Citations

PubMed

Rescue of primary ubiquinone deficiency due to a novel COQ7 defect using 2,4-dihydroxybensoic acid.

Freyer C, Stranneheim H, Naess K, Mourier A, Felser A, Maffezzini C, Lesko N, Bruhn H, Engvall M, Wibom R, Barbaro M, Hinze Y, Magnusson M, Andeer R, Zetterström RH, von Döbeln U, Wredenberg A, Wedell A.

J Med Genet. 2015 Nov;52(11):779-83. doi: 10.1136/jmedgenet-2015-102986. Epub 2015 Jun 17.

PubMed [citation]

PMID:: 26084283
PMCID:: PMC4680133

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, SCV000258602.3

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

Description

In a 9-year-old boy, born of consanguineous Syrian parents, with primary coenzyme Q10 deficiency-8 (COQ10D8; 616733), Freyer et al. (2015) identified a homozygous c.422T-A transversion (c.422T-A, NM_016138) in exon 4 of the COQ7 gene, resulting in a val141-to-glu (V141E) substitution at a highly conserved residue in the di-iron motif. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family, and was not found in public databases or in an in-house control database of 156 individuals. Mitochondrial extracts from patient skeletal muscle and fibroblasts showed severely decreased CoQ10 levels and a combined mitochondrial respiratory complex deficiency (about 40% maximal respiration) compared to controls. Treatment of patient cells with the CoQ10 analog 2,4-dihydroxybensoic acid (2,4DHB) was able to specifically bypass the COQ7 deficiency, increase cellular coenzyme Q10 levels, and rescue the biochemical defect in patient fibroblasts. Transfection of patient cells with wildtype CoQ7 also resulted in improved mitochondrial respiration.

#	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 Centre for Inherited Metabolic Diseases, Karolinska University Hospital, SCV004697822.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1		1	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	inherited	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Mar 10, 2024

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