Genetic Variant COQ8A:p.Ala337Ala (chr1-226982965-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_020247.5(COQ8A):c.1011C>T(p.Ala337Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000189 in 1,604,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A337A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

COQ8A
NM_020247.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -4.84

Publications

0 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: G2P, Orphanet
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 -13 ACMG points.

BP4

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

BP6

Variant 1-226982965-C-T is Benign according to our data. Variant chr1-226982965-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 446785.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.84 with no splicing effect.

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.1011C>T	p.Ala337Ala	synonymous	Exon 8 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.1011C>T	p.Ala337Ala	synonymous	Exon 8 of 15	ENSP00000355739.3	Q8NI60-1
COQ8A	ENST00000366778.5	TSL:1	c.855C>T	p.Ala285Ala	synonymous	Exon 8 of 15	ENSP00000355740.1	Q8NI60-3
ENSG00000288674	ENST00000366779.6	TSL:2	n.*5738C>T		non_coding_transcript_exon	Exon 25 of 32	ENSP00000355741.2

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000246

AC:

AN:

231354

AF XY:

0.000222

show subpopulations

Gnomad AFR exome

AF:

0.000212

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000207

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000451

Gnomad NFE exome

AF:

0.000370

Gnomad OTH exome

AF:

0.000350

GnomAD4 exome

AF:

0.000198

AC:

288

AN:

1452690

Hom.:

Cov.:

AF XY:

0.000190

AC XY:

137

AN XY:

722138

show subpopulations

African (AFR)

AF:

0.000180

AC:

AN:

33258

American (AMR)

AF:

0.00

AC:

AN:

43686

Ashkenazi Jewish (ASJ)

AF:

0.000154

AC:

AN:

25976

East Asian (EAS)

AF:

0.00

AC:

AN:

39070

South Asian (SAS)

AF:

0.000188

AC:

AN:

85262

European-Finnish (FIN)

AF:

0.000603

AC:

AN:

51404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.000198

AC:

220

AN:

1108344

Other (OTH)

AF:

0.000183

AC:

AN:

59992

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

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:

0.000105

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41454

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.000376

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68048

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.534

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:

0.000183

Hom.:

Bravo

AF:

0.000136

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

COQ8A-related disorder (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.087

(source)

DANN

Benign

0.74

PhyloP100

-4.8

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

3.7

Mutation Taster

=97/3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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