Variant chr6-99369637-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017421.4(COQ3):c.1073G>A(p.Cys358Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,614,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

COQ3
NM_017421.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.831

Variant links:

Genes affected

COQ3 (HGNC:18175): (coenzyme Q3, methyltransferase) Ubiquinone, also known as coenzyme Q, or Q, is a critical component of the electron transport pathways of both eukaryotes and prokaryotes (Jonassen and Clarke, 2000 [PubMed 10777520]). This lipid consists of a hydrophobic isoprenoid tail and a quinone head group. The tail varies in length depending on the organism, but its purpose is to anchor coenzyme Q to the membrane. The quinone head group is responsible for the activity of coenzyme Q in the respiratory chain. The S. cerevisiae COQ3 gene encodes an O-methyltransferase required for 2 steps in the biosynthetic pathway of coenzyme Q. This enzyme methylates an early coenzyme Q intermediate, 3,4-dihydroxy-5-polyprenylbenzoic acid, as well as the final intermediate in the pathway, converting demethyl-ubiquinone to coenzyme Q. The COQ3 gene product is also capable of methylating the distinct prokaryotic early intermediate 2-hydroxy-6-polyprenyl phenol.[supplied by OMIM, Mar 2008]

COQ3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.028922021).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COQ3	NM_017421.4 linkuse as main transcript	c.1073G>A	p.Cys358Tyr	missense_variant	7/7	ENST00000254759.8	NP_059117.3	Q9NZJ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COQ3	ENST00000254759.8 linkuse as main transcript	c.1073G>A	p.Cys358Tyr	missense_variant	7/7	1	NM_017421.4	ENSP00000254759.3		Q9NZJ6
COQ3	ENST00000369240.5 linkuse as main transcript	c.389G>A	p.Cys130Tyr	missense_variant	3/3	5		ENSP00000358243.1		F6WGP0

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000478

AC:

AN:

250954

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

135608

show subpopulations

Gnomad AFR exome

AF:

0.000738

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:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1461784

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

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:

0.00

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.000197

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.000698

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000347

Hom.:

Bravo

AF:

0.000136

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000576

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 09, 2021

The c.1073G>A (p.C358Y) alteration is located in exon 7 (coding exon 7) of the COQ3 gene. This alteration results from a G to A substitution at nucleotide position 1073, causing the cysteine (C) at amino acid position 358 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.68

CADD

Benign

8.5

DANN

Benign

0.47

DEOGEN2

Benign

0.025

T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.064

LIST_S2

Benign

0.44

T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.029

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

N;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.56

N;N

REVEL

Benign

0.023

Sift

Uncertain

0.027

D;D

Sift4G

Uncertain

0.019

D;D

Polyphen

0.43

B;.

Vest4

0.076

MVP

0.18

MPC

0.10

ClinPred

0.026

GERP RS

1.3

Varity_R

0.052

gMVP

0.29

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over