The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with clinical features associated with this gene. Assessment of experimental evidence suggests this variant may result in abnormal protein function. Studies showed this variant exhibited reduced protein function by failing to restore growth on selective respiratory medium (PMID: 18319074). This variant appears to segregate with disease in at least one family.
ClinVar Genomic variation as it relates to human health
NM_020247.5(COQ8A):c.1747ACC[1] (p.Thr584del)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(8)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Pathogenic/Likely pathogenic
8
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_020247.5(COQ8A):c.1747ACC[1] (p.Thr584del)
Variation ID: 3644 Accession: VCV000003644.19
- Type and length
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Microsatellite, 3 bp
- Location
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Cytogenetic: 1q42.13 1: 226986539-226986541 (GRCh38) [ NCBI UCSC ] 1: 227174240-227174242 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline May 29, 2016 Sep 16, 2024 Jan 18, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_020247.5:c.1747ACC[1] MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_064632.2:p.Thr584del inframe deletion NM_020247.5:c.1750_1752del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NC_000001.11:g.226986540ACC[1] NC_000001.10:g.227174241ACC[1] NG_012825.2:g.94005ACC[1] LRG_1092:g.94005ACC[1] LRG_1092t1:c.1747ACC[1] LRG_1092p1:p.Thr584del - Protein change
- T584del
- Other names
-
COQ8A, 3-BP DEL, 1750ACC
- Canonical SPDI
- NC_000001.11:226986538:CACCACC:CACC
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
- -
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| COQ8A | - | - |
GRCh38 GRCh37 |
716 | 760 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic/Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
|
Dec 17, 2021 | RCV000003829.21 | |
| Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Jan 18, 2024 | RCV000199676.21 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
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Pathogenic
(Aug 31, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Coenzyme Q10 deficiency, primary, 4
Affected status: yes
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV000593045.1
First in ClinVar: Nov 10, 2016 Last updated: Nov 10, 2016 |
|
|
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Pathogenic
(Feb 18, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Autosomal recessive ataxia due to ubiquinone deficiency
Affected status: yes
Allele origin:
maternal
|
Centogene AG - the Rare Disease Company
Accession: SCV002059708.1
First in ClinVar: Jan 15, 2022 Last updated: Jan 15, 2022 |
|
|
|
Likely pathogenic
(Dec 17, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Autosomal recessive ataxia due to ubiquinone deficiency
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV003829864.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
|
|
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Likely pathogenic
(Aug 18, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Athena Diagnostics
Accession: SCV002771176.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
Comment:
The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with … (more)
The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with clinical features associated with this gene. Assessment of experimental evidence suggests this variant may result in abnormal protein function. Studies showed this variant exhibited reduced protein function by failing to restore growth on selective respiratory medium (PMID: 18319074). This variant appears to segregate with disease in at least one family. (less)
|
|
|
Likely pathogenic
(Jan 18, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV002214128.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
This variant, c.1750_1752del, results in the deletion of 1 amino acid(s) of the COQ8A protein (p.Thr584del), but otherwise preserves the integrity of the reading frame. … (more)
This variant, c.1750_1752del, results in the deletion of 1 amino acid(s) of the COQ8A protein (p.Thr584del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has been observed in individual(s) with CoQ10 deficiency (PMID: 18319074, 27572814, 29915382, 30637285). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 3644). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects COQ8A function (PMID: 18319074, 26866375). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. (less)
|
|
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Likely pathogenic
(Dec 04, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000251077.13
First in ClinVar: Oct 11, 2015 Last updated: Sep 16, 2024 |
Comment:
In-frame deletion of 1 amino acid in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with … (more)
In-frame deletion of 1 amino acid in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22359546, 24048965, 27106809, 24218524, 31621627, 31589614, 32337771, 18319074, 20495179, 29431110, 29915382, 31078656, 31980526, 37476682, 27572814, 33677064, 30637285) (less)
|
|
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Pathogenic
(Mar 01, 2008)
|
no assertion criteria provided
Method: literature only
|
COENZYME Q10 DEFICIENCY, PRIMARY, 4
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000023994.3
First in ClinVar: Apr 04, 2013 Last updated: Sep 23, 2019 |
Comment on evidence:
For discussion of the 3-bp deletion (1750delACC) in the ADCK3 gene that was found in compound heterozygous state in an American boy with CoQ10 deficiency … (more)
For discussion of the 3-bp deletion (1750delACC) in the ADCK3 gene that was found in compound heterozygous state in an American boy with CoQ10 deficiency (COQ10D4; 612016) by Lagier-Tourenne et al. (2008), see 606980.0008. (less)
|
|
|
not provided
(-)
|
no classification provided
Method: literature only
|
Autosomal recessive ataxia due to ubiquinone deficiency
Affected status: unknown
Allele origin:
germline
|
GeneReviews
Accession: SCV000494106.2
First in ClinVar: Nov 10, 2016 Last updated: Oct 01, 2022 |
|
Comment:
Comment:
This variant, c.1750_1752del, results in the deletion of 1 amino acid(s) of the COQ8A protein (p.Thr584del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has been observed in individual(s) with CoQ10 deficiency (PMID: 18319074, 27572814, 29915382, 30637285). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 3644). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects COQ8A function (PMID: 18319074, 26866375). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Comment:
In-frame deletion of 1 amino acid in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22359546, 24048965, 27106809, 24218524, 31621627, 31589614, 32337771, 18319074, 20495179, 29431110, 29915382, 31078656, 31980526, 37476682, 27572814, 33677064, 30637285)
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with clinical features associated with this gene. Assessment of experimental evidence suggests this variant may result in abnormal protein function. Studies showed this variant exhibited reduced protein function by failing to restore growth on selective respiratory medium (PMID: 18319074). This variant appears to segregate with disease in at least one family.
Comment:
This variant, c.1750_1752del, results in the deletion of 1 amino acid(s) of the COQ8A protein (p.Thr584del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has been observed in individual(s) with CoQ10 deficiency (PMID: 18319074, 27572814, 29915382, 30637285). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 3644). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects COQ8A function (PMID: 18319074, 26866375). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Comment:
In-frame deletion of 1 amino acid in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22359546, 24048965, 27106809, 24218524, 31621627, 31589614, 32337771, 18319074, 20495179, 29431110, 29915382, 31078656, 31980526, 37476682, 27572814, 33677064, 30637285)
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Primary Coenzyme Q(10) Deficiency Overview. | Adam MP | - | 2023 | PMID: 28125198 |
| Clinico-Genetic, Imaging and Molecular Delineation of COQ8A-Ataxia: A Multicenter Study of 59 Patients. | Traschütz A | Annals of neurology | 2020 | PMID: 32337771 |
| Targeted exome analysis identifies the genetic basis of disease in over 50% of patients with a wide range of ataxia-related phenotypes. | Sun M | Genetics in medicine : official journal of the American College of Medical Genetics | 2019 | PMID: 29915382 |
| ADCK3-related Coenzyme Q10 Deficiency: A Potentially Treatable Genetic Disease. | Chang A | Movement disorders clinical practice | 2018 | PMID: 30637285 |
| Utility of Whole Exome Sequencing for Genetic Diagnosis of Previously Undiagnosed Pediatric Neurology Patients. | Kuperberg M | Journal of child neurology | 2016 | PMID: 27572814 |
| AarF Domain Containing Kinase 3 (ADCK3) Mutant Cells Display Signs of Oxidative Stress, Defects in Mitochondrial Homeostasis and Lysosomal Accumulation. | Cullen JK | PloS one | 2016 | PMID: 26866375 |
| Heterozygous Mutations in the ADCK3 Gene in Siblings with Cerebellar Atrophy and Extreme Phenotypic Variability. | Blumkin L | JIMD reports | 2014 | PMID: 24048965 |
| Effects of inhibiting CoQ10 biosynthesis with 4-nitrobenzoate in human fibroblasts. | Quinzii CM | PloS one | 2012 | PMID: 22359546 |
| ADCK3, an ancestral kinase, is mutated in a form of recessive ataxia associated with coenzyme Q10 deficiency. | Lagier-Tourenne C | American journal of human genetics | 2008 | PMID: 18319074 |
| Cerebellar ataxia and coenzyme Q10 deficiency. | Lamperti C | Neurology | 2003 | PMID: 12682339 |
Text-mined citations for rs387906299 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Oct 27, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.