1-226965120-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_020247.5(COQ8A):c.298G>T(p.Asp100Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000408 in 1,613,938 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D100N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0018 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00026 ( 2 hom. )

Consequence

COQ8A
NM_020247.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.0980

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive ataxia due to ubiquinone deficiency
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
coenzyme Q10 deficiency
Inheritance: AR Classification: DEFINITIVE Submitted by: Illumina

COQ8A links:

ENSG00000288674 (HGNC:):

ENSG00000288674 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005143672).

BP6

Variant 1-226965120-G-T is Benign according to our data. Variant chr1-226965120-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 214027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0018 (274/152340) while in subpopulation AFR AF = 0.00577 (240/41574). AF 95% confidence interval is 0.00517. There are 3 homozygotes in GnomAd4. There are 133 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020247.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COQ8A	NM_020247.5	MANE Select	c.298G>T	p.Asp100Tyr	missense	Exon 3 of 15	NP_064632.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COQ8A	ENST00000366777.4	TSL:1 MANE Select	c.298G>T	p.Asp100Tyr	missense	Exon 3 of 15	ENSP00000355739.3	Q8NI60-1
COQ8A	ENST00000366778.5	TSL:1	c.142G>T	p.Asp48Tyr	missense	Exon 3 of 15	ENSP00000355740.1	Q8NI60-3
ENSG00000288674	ENST00000366779.6	TSL:2	n.*5025G>T		non_coding_transcript_exon	Exon 20 of 32	ENSP00000355741.2

Frequencies

GnomAD3 genomes

AF:

0.00176

AC:

268

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00565

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.000649

AC:

163

AN:

251052

AF XY:

0.000530

show subpopulations

Gnomad AFR exome

AF:

0.00611

Gnomad AMR exome

AF:

0.000723

Gnomad ASJ exome

AF:

0.00259

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000793

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000263

AC:

384

AN:

1461598

Hom.:

Cov.:

AF XY:

0.000241

AC XY:

175

AN XY:

727098

show subpopulations

African (AFR)

AF:

0.00460

AC:

154

AN:

33480

American (AMR)

AF:

0.000716

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00329

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53140

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000414

AC:

AN:

1112008

Other (OTH)

AF:

0.000994

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

103

138

172

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00180

AC:

274

AN:

152340

Hom.:

Cov.:

AF XY:

0.00179

AC XY:

133

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.00577

AC:

240

AN:

41574

American (AMR)

AF:

0.000653

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68024

Other (OTH)

AF:

0.00237

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000732

Hom.:

Bravo

AF:

0.00210

ESP6500AA

AF:

0.00704

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000725

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Autosomal recessive ataxia due to ubiquinone deficiency (1)

COQ8A-related disorder (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.74

DEOGEN2

Benign

0.11

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.43

M_CAP

Benign

0.065

MetaRNN

Benign

0.0051

MetaSVM

Benign

-0.84

PhyloP100

-0.098

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.96

REVEL

Benign

0.25

Sift

Benign

0.057

Sift4G

Uncertain

0.051

Polyphen

0.53

Vest4

0.30

MVP

0.20

MPC

0.079

ClinPred

0.0084

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.036

gMVP

0.38

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over