rs113667144

Positions:

• chr1-226965062-C-G
• chr1-226965062-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020247.5(COQ8A):​c.240C>G​(p.His80Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. 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. H80Y) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: COQ8A NM_020247.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.986

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.072273046).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COQ8A	NM_020247.5	c.240C>G	p.His80Gln	missense_variant	3/15	ENST00000366777.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COQ8A	ENST00000366777.4	c.240C>G	p.His80Gln	missense_variant	3/15	1	NM_020247.5	P1
COQ8A	ENST00000366778.5	c.84C>G	p.His28Gln	missense_variant	3/15	1
COQ8A	ENST00000489044.1	n.451C>G		non_coding_transcript_exon_variant	3/5	3
COQ8A	ENST00000478406.5	n.107-12387C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	9.8
DANN	Benign	0.41
DEOGEN2	Benign	0.055	T;.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.87
FATHMM_MKL	Uncertain	0.85	D
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.072	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D;D;N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.51	N;N;N
REVEL	Benign	0.12
Sift	Benign	0.59	T;T;T
Sift4G	Benign	0.57	T;T;T
Polyphen		0.0010	B;.;B
Vest4		0.073
MutPred		0.14		Loss of sheet (P = 0.0817);.;Loss of sheet (P = 0.0817);
MVP		0.38
MPC		0.044
ClinPred		0.025	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.023
gMVP		0.18

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

Other links and lift over

dbSNP: rs113667144; hg19: chr1-227152763;