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

gnomAD frequency: 0.01390  dbSNP: rs41303129

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000415784	SCV000166878	benign	not provided	2018-12-04	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 26764160, 27884173, 27535533, 18319074, 32337771)
Eurofins Ntd Llc (ga)	RCV000180351	SCV000232764	benign	not specified	2014-12-17	criteria provided, single submitter	clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000180351	SCV000258150	benign	not specified	2015-04-12	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000003830	SCV000355249	benign	Autosomal recessive ataxia due to ubiquinone deficiency	2018-03-06	criteria provided, single submitter	clinical testing	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.
CeGaT Center for Human Genetics Tuebingen	RCV000415784	SCV000493421	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	COQ8A: BP4, BP7, BS1, BS2
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000180351	SCV000538237	benign	not specified	2016-03-29	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: frequency in ExAC 2.8% in european population with (24 homozygotes). Also Benign in Clinvar (by GeneDx and Emory)
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000003830	SCV000884981	benign	Autosomal recessive ataxia due to ubiquinone deficiency	2023-06-28	criteria provided, single submitter	clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001258271	SCV001435196	benign	Joubert syndrome 17		criteria provided, single submitter	research	The c.993C>T (p.Phe331=) variant in ADCK3 has been identified in a French and Algerian individual with ubiquinone deficiency with cerebellar ataxia (PMID: 18319074), but has also been identified in >4% of European (Finnish) chromosomes and 33 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In vitro functional studies provide some evidence that the c.993C>T variant may not impact protein function (PMID: 18319074). However, these types of assays may not accurately represent biological function. In summary, this variant meets criteria to be classified as benign for autosomal recessive ubiquinone deficiency with cerebellar ataxia.
Invitae	RCV000415784	SCV001724874	benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000003830	SCV002803569	benign	Autosomal recessive ataxia due to ubiquinone deficiency	2021-07-20	criteria provided, single submitter	clinical testing
OMIM	RCV000003830	SCV000023995	pathogenic	Autosomal recessive ataxia due to ubiquinone deficiency	2008-03-01	no assertion criteria provided	literature only
GeneReviews	RCV000003830	SCV000494096	not provided	Autosomal recessive ataxia due to ubiquinone deficiency		no assertion provided	literature only
Mayo Clinic Laboratories, Mayo Clinic	RCV000415784	SCV000801931	benign	not provided	2016-02-25	no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000180351	SCV001742409	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000180351	SCV001924656	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000415784	SCV001931737	likely benign	not provided		no assertion criteria provided	clinical testing