4-83284628-G-T

Variant names:

• chr4-83284628-G-T
• NM_001358921.2:c.137C>A

Variant summary

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

The NM_001358921.2(COQ2):​c.137C>A​(p.Pro46His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000734 in 1,362,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 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. P46L) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: COQ2 NM_001358921.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.979

Genes affected

COQ2 (HGNC:25223): (coenzyme Q2, polyprenyltransferase) This gene encodes an enzyme that functions in the final steps in the biosynthesis of CoQ (ubiquinone), a redox carrier in the mitochondrial respiratory chain and a lipid-soluble antioxidant. This enzyme, which is part of the coenzyme Q10 pathway, catalyzes the prenylation of parahydroxybenzoate with an all-trans polyprenyl group. Mutations in this gene cause coenzyme Q10 deficiency, a mitochondrial encephalomyopathy, and also COQ2 nephropathy, an inherited form of mitochondriopathy with primary renal involvement. [provided by RefSeq, Oct 2009]

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=0.19525415).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COQ2	NM_001358921.2	c.137C>A	p.Pro46His	missense_variant	Exon 1 of 7	ENST00000647002.2	NP_001345850.1
COQ2	NM_015697.9	c.287C>A	p.Pro96His	missense_variant	Exon 1 of 7		NP_056512.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COQ2	ENST00000647002.2	c.137C>A	p.Pro46His	missense_variant	Exon 1 of 7		NM_001358921.2	ENSP00000495761.2
COQ2	ENST00000311469.9	c.287C>A	p.Pro96His	missense_variant	Exon 1 of 7	1		ENSP00000310873.4
COQ2	ENST00000311461.7	c.137C>A	p.Pro46His	missense_variant	Exon 1 of 7	5		ENSP00000311835.7
COQ2	ENST00000503391.5	n.137C>A		non_coding_transcript_exon_variant	Exon 1 of 7	2		ENSP00000426242.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.34e-7 AC: 1 AN: 1362520 Hom.: 0 Cov.: 84 AF XY: 0.00 AC XY: 0 AN XY: 671566

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: 0.00

Gnomad4 NFE exome AF: 9.39e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.073	.;.;T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.30	T;.;T
M_CAP	Pathogenic	0.73	D
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-0.72	T
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.31	.;N;N
REVEL	Benign	0.11
Sift	Uncertain	0.024	.;D;T
Sift4G	Uncertain	0.011	.;D;D
Polyphen		0.41	.;.;B
Vest4		0.21, 0.26
MutPred		0.29		Loss of catalytic residue at P45 (P = 0.016);.;Loss of catalytic residue at P45 (P = 0.016);
MVP		0.87
MPC		0.27
ClinPred		0.26	T
GERP RS		-0.27
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
gMVP		0.32

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-84205781;