NM_020247.5(COQ8A):c.993C>T (p.Phe331=) AND Autosomal recessive ataxia due to ubiquinone deficiency

Germline classification:: Benign (5 submissions)
Last evaluated:: Jun 28, 2023
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:: RCV000003830.23

Allele description [Variation Report for NM_020247.5(COQ8A):c.993C>T (p.Phe331=)]

NM_020247.5(COQ8A):c.993C>T (p.Phe331=)

Gene:

COQ8A:coenzyme Q8A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q42.13

Genomic location:

Preferred name:

NM_020247.5(COQ8A):c.993C>T (p.Phe331=)

Other names:

p.F331F:TTC>TTT

HGVS:

NC_000001.11:g.226982947C>T
NG_012825.2:g.90412C>T
NM_020247.5:c.993C>TMANE SELECT
NP_064632.2:p.Phe331=
LRG_1092t1:c.993C>T
LRG_1092:g.90412C>T
LRG_1092p1:p.Phe331=
NC_000001.10:g.227170648C>T
NG_012825.1:g.47711C>T
NM_020247.4:c.993C>T
NP_064632.2:p.Leu314_Gln360del
p.Phe331Phe

Links:

OMIM: 606980.0010; dbSNP: rs41303129

NCBI 1000 Genomes Browser:

rs41303129

Molecular consequence:

NM_020247.5:c.993C>T - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:: Autosomal recessive ataxia due to ubiquinone deficiency
Synonyms:: Spinocerebellar ataxia, autosomal recessive 9; Coenzyme Q10 deficiency, primary, 4
Identifiers:: MONDO: MONDO:0012784; MedGen: C2677589; Orphanet: 139485; OMIM: 612016

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000023995	OMIM	no assertion criteria provided	Pathogenic (Mar 1, 2008)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000355249	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Benign (Mar 6, 2018)	germline	clinical testing	Citation Link,
SCV000494096	GeneReviews	no classification provided	not provided	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000884981	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	Benign (Jun 28, 2023)	germline	clinical testing	Citation Link,
SCV002803569	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Jul 20, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

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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, literature only

Citations

PubMed

ADCK3, an ancestral kinase, is mutated in a form of recessive ataxia associated with coenzyme Q10 deficiency.

Lagier-Tourenne C, Tazir M, López LC, Quinzii CM, Assoum M, Drouot N, Busso C, Makri S, Ali-Pacha L, Benhassine T, Anheim M, Lynch DR, Thibault C, Plewniak F, Bianchetti L, Tranchant C, Poch O, DiMauro S, Mandel JL, Barros MH, Hirano M, Koenig M.

Am J Hum Genet. 2008 Mar;82(3):661-72. doi: 10.1016/j.ajhg.2007.12.024.

PubMed [citation]

PMID:: 18319074
PMCID:: PMC2427193

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, SCV000023995.3

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

Description

In a patient of French and Algerian ancestry with CoQ10 deficiency-4 manifest as cerebellar ataxia (COQ10D4; 612016), Lagier-Tourenne et al. (2008) found compound heterozygosity for 2 mutations in the ADCK3 gene: a mutation in a predicted exonic splice enhancer in exon 8 (993C-T), and a 1645G-A transition in exon 14, resulting in a gly549-to-ser substitution (G549S; 606980.0011). The exon 8 mutation resulted in skipping of exon 8 leading to an in-frame deletion of 47 amino acids (Lys314_Gln360del).

#	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 Illumina Laboratory Services, Illumina, SCV000355249.3

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

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

#	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 GeneReviews, SCV000494096.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	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 ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000884981.5

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

#	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, SCV002803569.1

#	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: Oct 20, 2024

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