Variant 1-226982954-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PM5

The ENST00000366777.4(COQ8A):c.1000C>G(p.Arg334Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000962 in 1,455,102 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R334W) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

COQ8A
ENST00000366777.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.88

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM1

In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 1 benign, 8 uncertain in ENST00000366777.4

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr1-226982954-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 434088.We mark this variant Likely_pathogenic, oryginal submissions are: {Likely_pathogenic=2, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COQ8A	NM_020247.5 linkuse as main transcript	c.1000C>G	p.Arg334Gly	missense_variant	8/15	ENST00000366777.4	NP_064632.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COQ8A	ENST00000366777.4 linkuse as main transcript	c.1000C>G	p.Arg334Gly	missense_variant	8/15	1	NM_020247.5	ENSP00000355739	P1	Q8NI60-1
COQ8A	ENST00000366778.5 linkuse as main transcript	c.844C>G	p.Arg282Gly	missense_variant	8/15	1		ENSP00000355740		Q8NI60-3
COQ8A	ENST00000485462.5 linkuse as main transcript	n.390C>G		non_coding_transcript_exon_variant	4/11	1
COQ8A	ENST00000478406.5 linkuse as main transcript	n.979C>G		non_coding_transcript_exon_variant	4/8	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000169

AC:

AN:

236112

Hom.:

AF XY:

0.00

AC XY:

AN XY:

128978

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000147

Gnomad NFE exome

AF:

0.00000953

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000962

AC:

AN:

1455102

Hom.:

Cov.:

AF XY:

0.00000553

AC XY:

AN XY:

723546

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000253

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000166

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Uncertain

0.056

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.46

T;.;T

Eigen

Benign

0.040

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.87

.;D;D

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.55

D;D;D

MetaSVM

Benign

-0.90

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-4.4

D;D;D

REVEL

Benign

0.24

Sift

Benign

0.047

D;T;D

Sift4G

Benign

0.081

T;T;T

Polyphen

0.016

B;.;B

Vest4

0.64

MutPred

0.53

Gain of catalytic residue at R334 (P = 0.0757);.;Gain of catalytic residue at R334 (P = 0.0757);

MVP

0.51

MPC

0.060

ClinPred

0.69

GERP RS

4.7

Varity_R

0.91

gMVP

0.80

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over