1-226961463-C-T

Variant names:

Variant summary

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

The NM_020247.5(COQ8A):c.78C>T(p.His26His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000334 in 1,613,896 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

COQ8A
NM_020247.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.736

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=-0.52).

BP6

Variant 1-226961463-C-T is Benign according to our data. Variant chr1-226961463-C-T is described in ClinVar as [Benign]. Clinvar id is 136296.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-226961463-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.736 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00192 (293/152378) while in subpopulation AFR AF= 0.00656 (273/41594). AF 95% confidence interval is 0.00592. There are 3 homozygotes in gnomad4. There are 148 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COQ8A	NM_020247.5 link	c.78C>T	p.His26His	synonymous_variant	Exon 2 of 15	ENST00000366777.4	NP_064632.2	Q8NI60-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
COQ8A	ENST00000366777.4 link	c.78C>T	p.His26His	synonymous_variant	Exon 2 of 15	1	NM_020247.5	ENSP00000355739.3	Q8NI60-1
ENSG00000288674	ENST00000366779.6 link	n.*4805C>T		non_coding_transcript_exon_variant	Exon 19 of 32	2		ENSP00000355741.2
ENSG00000288674	ENST00000366779.6 link	n.*4805C>T		3_prime_UTR_variant	Exon 19 of 32	2		ENSP00000355741.2

Frequencies

GnomAD3 genomes

AF:

0.00193

AC:

294

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00658

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.000478

AC:

120

AN:

251124

Hom.:

AF XY:

0.000324

AC XY:

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.00641

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000441

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000168

AC:

246

AN:

1461518

Hom.:

Cov.:

AF XY:

0.000144

AC XY:

105

AN XY:

727074

show subpopulations

Gnomad4 AFR exome

AF:

0.00600

Gnomad4 AMR exome

AF:

0.000402

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.00000629

Gnomad4 OTH exome

AF:

0.000281

GnomAD4 genome

AF:

0.00192

AC:

293

AN:

152378

Hom.:

Cov.:

AF XY:

0.00199

AC XY:

148

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00656

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.000867

Hom.:

Bravo

AF:

0.00235

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Apr 22, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Feb 20, 2020

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

6.3

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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