1-226982902-C-T

Position:

chr1-226982902-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_020247.5(COQ8A):c.948C>T(p.Leu316Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00229 in 1,612,792 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 2 hom., cov: 34)

Exomes 𝑓: 0.0023 ( 7 hom. )

Consequence

COQ8A
NM_020247.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.446

Variant links:

Genes affected

COQ8A (HGNC:16812): (coenzyme Q8A) This gene encodes a mitochondrial protein similar to yeast ABC1, which functions in an electron-transferring membrane protein complex in the respiratory chain. It is not related to the family of ABC transporter proteins. Expression of this gene is induced by the tumor suppressor p53 and in response to DNA damage, and inhibiting its expression partially suppresses p53-induced apoptosis. Alternatively spliced transcript variants have been found; however, their full-length nature has not been determined. [provided by RefSeq, Jul 2008]

COQ8A links:

ENSG00000288674 (HGNC:):

ENSG00000288674 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 1-226982902-C-T is Benign according to our data. Variant chr1-226982902-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 136301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-226982902-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.446 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00217 (330/152352) while in subpopulation AMR AF= 0.00346 (53/15310). AF 95% confidence interval is 0.00272. There are 2 homozygotes in gnomad4. There are 156 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COQ8A	NM_020247.5 linkuse as main transcript	c.948C>T	p.Leu316Leu	synonymous_variant	8/15	ENST00000366777.4	NP_064632.2	Q8NI60-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
COQ8A	ENST00000366777.4 linkuse as main transcript	c.948C>T	p.Leu316Leu	synonymous_variant	8/15	1	NM_020247.5	ENSP00000355739.3	Q8NI60-1
ENSG00000288674	ENST00000366779.6 linkuse as main transcript	n.*5675C>T		non_coding_transcript_exon_variant	25/32	2		ENSP00000355741.2
ENSG00000288674	ENST00000366779.6 linkuse as main transcript	n.*5675C>T		3_prime_UTR_variant	25/32	2		ENSP00000355741.2

Frequencies

GnomAD3 genomes

AF:

0.00216

AC:

329

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00347

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000413

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00284

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00218

AC:

542

AN:

248836

Hom.:

AF XY:

0.00245

AC XY:

331

AN XY:

135176

show subpopulations

Gnomad AFR exome

AF:

0.000188

Gnomad AMR exome

AF:

0.00148

Gnomad ASJ exome

AF:

0.0106

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000687

Gnomad FIN exome

AF:

0.00219

Gnomad NFE exome

AF:

0.00265

Gnomad OTH exome

AF:

0.00280

GnomAD4 exome

AF:

0.00230

AC:

3359

AN:

1460440

Hom.:

Cov.:

AF XY:

0.00232

AC XY:

1683

AN XY:

726496

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.00175

Gnomad4 ASJ exome

AF:

0.00995

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000997

Gnomad4 FIN exome

AF:

0.00256

Gnomad4 NFE exome

AF:

0.00237

Gnomad4 OTH exome

AF:

0.00253

GnomAD4 genome

AF:

0.00217

AC:

330

AN:

152352

Hom.:

Cov.:

AF XY:

0.00209

AC XY:

156

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.000264

Gnomad4 AMR

AF:

0.00346

Gnomad4 ASJ

AF:

0.0118

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.00284

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00247

Hom.:

Bravo

AF:

0.00193

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00393

EpiControl

AF:

0.00320

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:6

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	COQ8A: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 24, 2024	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Dec 30, 2017	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 08, 2013

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

COQ8A-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 28, 2021

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

1.1

DANN

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over