Genetic Variant NM_020247.5:c.1014C>T (chr1-226982968-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.1014C>T(p.Ala338Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000361 in 1,604,508 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 (★★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

COQ8A
NM_020247.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -8.99

Publications

1 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 1-226982968-C-T is Benign according to our data. Variant chr1-226982968-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 585372.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-8.99 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COQ8A	NM_020247.5 link	c.1014C>T	p.Ala338Ala	synonymous_variant	Exon 8 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.1014C>T	p.Ala338Ala	synonymous_variant	Exon 8 of 15	1	NM_020247.5	ENSP00000355739.3	Q8NI60-1
ENSG00000288674	ENST00000366779.6 link	n.*5741C>T		non_coding_transcript_exon_variant	Exon 25 of 32	2		ENSP00000355741.2
ENSG00000288674	ENST00000366779.6 link	n.*5741C>T		3_prime_UTR_variant	Exon 25 of 32	2		ENSP00000355741.2

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000651

AC:

AN:

230426

AF XY:

0.0000796

show subpopulations

Gnomad AFR exome

AF:

0.000285

Gnomad AMR exome

AF:

0.0000304

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000503

Gnomad NFE exome

AF:

0.0000195

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000317

AC:

AN:

1452166

Hom.:

Cov.:

AF XY:

0.0000443

AC XY:

AN XY:

721848

show subpopulations

African (AFR)

AF:

0.0000301

AC:

AN:

33220

American (AMR)

AF:

0.0000229

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:

0.000188

AC:

AN:

85178

European-Finnish (FIN)

AF:

0.0000195

AC:

AN:

51384

Middle Eastern (MID)

AF:

0.000352

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

0.0000217

AC:

AN:

1108128

Other (OTH)

AF:

0.0000167

AC:

AN:

59974

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

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:

0.0000788

AC:

AN:

152342

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.000216

AC:

AN:

41590

American (AMR)

AF:

0.0000653

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000194

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

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:

0.0000868

Hom.:

Bravo

AF:

0.0000604

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 21, 2017

Athena Diagnostics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 09, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely 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

-0.83

CADD

Benign

0.025

(source)

DANN

Benign

0.72

PhyloP100

-9.0

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over