Genetic Variant NM_020247.5:c.1014C>A (chr1-226982968-C-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_020247.5(COQ8A):c.1014C>A(p.Ala338Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,452,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A338A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

COQ8A
NM_020247.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -8.99

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: Orphanet, G2P
coenzyme Q10 deficiency
Inheritance: AR Classification: DEFINITIVE Submitted by: Illumina

COQ8A links:

ENSG00000288674 (HGNC:):

ENSG00000288674 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP7

Synonymous conserved (PhyloP=-8.99 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.1014C>A	p.Ala338Ala	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.1014C>A	p.Ala338Ala	synonymous	Exon 8 of 15	ENSP00000355739.3	Q8NI60-1
COQ8A	ENST00000366778.5	TSL:1	c.858C>A	p.Ala286Ala	synonymous	Exon 8 of 15	ENSP00000355740.1	Q8NI60-3
ENSG00000288674	ENST00000366779.6	TSL:2	n.*5741C>A		non_coding_transcript_exon	Exon 25 of 32	ENSP00000355741.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1452166

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721848

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33220

American (AMR)

AF:

0.00

AC:

AN:

43602

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25968

East Asian (EAS)

AF:

0.00

AC:

AN:

39024

South Asian (SAS)

AF:

0.00

AC:

AN:

85178

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51384

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

9.02e-7

AC:

AN:

1108128

Other (OTH)

AF:

0.00

AC:

AN:

59974

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.0050

(source)

DANN

Benign

0.64

PhyloP100

-9.0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over