NM_020247.5(COQ8A):c.1665G>A (p.Met555Ile) AND Autosomal recessive ataxia due to ubiquinone deficiency

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 3, 2018
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:: RCV000778972.6

Allele description [Variation Report for NM_020247.5(COQ8A):c.1665G>A (p.Met555Ile)]

NM_020247.5(COQ8A):c.1665G>A (p.Met555Ile)

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.1665G>A (p.Met555Ile)

HGVS:

NC_000001.11:g.226986458G>A
NG_012825.2:g.93923G>A
NM_020247.5:c.1665G>AMANE SELECT
NP_064632.2:p.Met555Ile
LRG_1092t1:c.1665G>A
LRG_1092:g.93923G>A
LRG_1092p1:p.Met555Ile
NC_000001.10:g.227174159G>A
NM_020247.4:c.1665G>A

Protein change:

M555I

Links:

dbSNP: rs199874519

NCBI 1000 Genomes Browser:

rs199874519

Molecular consequence:

NM_020247.5:c.1665G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000915400	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 09 May 2019)	Uncertain significance (Dec 3, 2018)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25280894, 25131622, 25356970 Citation Link,
SCV004041767	Zotz-Klimas Genetics Lab, MVZ Zotz Klimas	no assertion criteria provided	Likely pathogenic (Oct 9, 2023)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000915400

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 09 May 2019)

Uncertain significance
(Dec 3, 2018)

germline

clinical testing

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

Citation Link,

SCV004041767

Zotz-Klimas Genetics Lab, MVZ Zotz Klimas

no assertion criteria provided

Likely pathogenic
(Oct 9, 2023)

germline

clinical testing

Help

Summary from all submissions

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

Citations

PubMed

A diagnostic approach for cerebral palsy in the genomic era.

Lee RW, Poretti A, Cohen JS, Levey E, Gwynn H, Johnston MV, Hoon AH, Fatemi A.

Neuromolecular Med. 2014 Dec;16(4):821-44. doi: 10.1007/s12017-014-8331-9. Epub 2014 Oct 4.

PubMed [citation]

PMID:: 25280894
PMCID:: PMC4229412

Clinical whole exome sequencing in child neurology practice.

Srivastava S, Cohen JS, Vernon H, Barañano K, McClellan R, Jamal L, Naidu S, Fatemi A.

Ann Neurol. 2014 Oct;76(4):473-83. doi: 10.1002/ana.24251. Epub 2014 Aug 30.

PubMed [citation]

PMID:: 25131622

See all PubMed Citations (3)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000915400.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The ADCK3 c.1665G>A (p.Met555Ile) missense variant has been reported in three studies all describing the same individual diagnosed with coenzyme Q10 deficiency, with spinocerebellar ataxia (Srivastava et al. 2014; Lee et al. 2014; Farwell et al. 2015). The variant was found in a compound heterozygous state with a second missense variant. Control data are unavailable for the p.Met555Ile variant which is reported at a frequency of 0.000795 in the European (Finnish) population of the Genome Aggregation Database. Based on the limited evidence, the p.Met555Ile variant is classified as a variant of unknown significance, but suspicious for pathogenicity for coenzyme Q10 deficiency, spinocerebellar ataxia type. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

#	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 Zotz-Klimas Genetics Lab, MVZ Zotz Klimas, SCV004041767.1

#	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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 15, 2024

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