1-226961447-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_020247.5(COQ8A):c.62C>T(p.Ala21Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,613,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A21E) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000098 ( 0 hom. )

Consequence

COQ8A
NM_020247.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 1.20

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: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.036584944).

BP6

Variant 1-226961447-C-T is Benign according to our data. Variant chr1-226961447-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 214025.

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.62C>T	p.Ala21Val	missense	Exon 2 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.62C>T	p.Ala21Val	missense	Exon 2 of 15	ENSP00000355739.3	Q8NI60-1
COQ8A	ENST00000366778.5	TSL:1	c.-34-61C>T		intron	N/A	ENSP00000355740.1	Q8NI60-3
ENSG00000288674	ENST00000366779.6	TSL:2	n.*4789C>T		non_coding_transcript_exon	Exon 19 of 32	ENSP00000355741.2

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000131

AC:

AN:

251130

AF XY:

0.000133

show subpopulations

Gnomad AFR exome

AF:

0.000555

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000462

Gnomad NFE exome

AF:

0.0000529

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000978

AC:

143

AN:

1461450

Hom.:

Cov.:

AF XY:

0.0000949

AC XY:

AN XY:

727042

show subpopulations

African (AFR)

AF:

0.000717

AC:

AN:

33480

American (AMR)

AF:

0.000268

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

52992

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000683

AC:

AN:

1112004

Other (OTH)

AF:

0.000132

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

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:

0.000256

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.000746

AC:

AN:

41582

American (AMR)

AF:

0.000131

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

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:

0.000350

Hom.:

Bravo

AF:

0.000276

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000132

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.73

M_CAP

Benign

0.039

MetaRNN

Benign

0.037

MetaSVM

Benign

-0.65

PhyloP100

1.2

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.1

REVEL

Benign

0.21

Sift

Benign

0.12

Sift4G

Benign

0.18

Polyphen

0.080

Vest4

0.33

MVP

0.68

MPC

0.047

ClinPred

0.012

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.054

gMVP

0.58

Mutation Taster

=88/12

polymorphism

(source)

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

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