Variant rs3742049 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032314.4(COQ5):c.454G>A(p.Ala152Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,613,768 control chromosomes in the GnomAD database, including 11,549 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.15 ( 1951 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9598 hom. )

Consequence

COQ5
NM_032314.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.328

Variant links:

Genes affected

COQ5 (HGNC:28722): (coenzyme Q5, methyltransferase) Enables 2-octaprenyl-6-methoxy-1,4-benzoquinone methylase activity. Involved in methylation and ubiquinone biosynthetic process. Located in mitochondrial matrix. Part of protein-containing complex. Colocalizes with mitochondrial inner membrane. Implicated in primary coenzyme Q10 deficiency 9. [provided by Alliance of Genome Resources, Apr 2022]

COQ5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016256571).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COQ5	NM_032314.4 linkuse as main transcript	c.454G>A	p.Ala152Thr	missense_variant	3/7	ENST00000288532.11	NP_115690.3
COQ5	XM_006719639.3 linkuse as main transcript	c.211G>A	p.Ala71Thr	missense_variant	4/8		XP_006719702.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COQ5	ENST00000288532.11 linkuse as main transcript	c.454G>A	p.Ala152Thr	missense_variant	3/7	1	NM_032314.4	ENSP00000288532	P1

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22370

AN:

151966

Hom.:

1940

Cov.:

show subpopulations

Gnomad AFR

AF:

0.244

Gnomad AMI

AF:

0.0647

Gnomad AMR

AF:

0.122

Gnomad ASJ

AF:

0.0602

Gnomad EAS

AF:

0.0682

Gnomad SAS

AF:

0.0775

Gnomad FIN

AF:

0.132

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.117

GnomAD3 exomes

AF:

0.114

AC:

28584

AN:

251496

Hom.:

1925

AF XY:

0.109

AC XY:

14769

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.255

Gnomad AMR exome

AF:

0.108

Gnomad ASJ exome

AF:

0.0690

Gnomad EAS exome

AF:

0.0659

Gnomad SAS exome

AF:

0.0787

Gnomad FIN exome

AF:

0.126

Gnomad NFE exome

AF:

0.115

Gnomad OTH exome

AF:

0.0940

GnomAD4 exome

AF:

0.110

AC:

161033

AN:

1461684

Hom.:

9598

Cov.:

AF XY:

0.109

AC XY:

79029

AN XY:

727144

show subpopulations

Gnomad4 AFR exome

AF:

0.253

Gnomad4 AMR exome

AF:

0.108

Gnomad4 ASJ exome

AF:

0.0649

Gnomad4 EAS exome

AF:

0.0681

Gnomad4 SAS exome

AF:

0.0785

Gnomad4 FIN exome

AF:

0.127

Gnomad4 NFE exome

AF:

0.110

Gnomad4 OTH exome

AF:

0.107

GnomAD4 genome

AF:

0.147

AC:

22423

AN:

152084

Hom.:

1951

Cov.:

AF XY:

0.146

AC XY:

10859

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.245

Gnomad4 AMR

AF:

0.122

Gnomad4 ASJ

AF:

0.0602

Gnomad4 EAS

AF:

0.0683

Gnomad4 SAS

AF:

0.0778

Gnomad4 FIN

AF:

0.132

Gnomad4 NFE

AF:

0.114

Gnomad4 OTH

AF:

0.116

Alfa

AF:

0.115

Hom.:

2655

Bravo

AF:

0.148

TwinsUK

AF:

0.102

AC:

378

ALSPAC

AF:

0.110

AC:

425

ESP6500AA

AF:

0.252

AC:

1112

ESP6500EA

AF:

0.108

AC:

927

ExAC

AF:

0.118

AC:

14379

Asia WGS

AF:

0.108

AC:

377

AN:

3478

EpiCase

AF:

0.106

EpiControl

AF:

0.105

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.060

T;T;T;T

Eigen

Benign

-0.044

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.74

T;T;T;T

MetaRNN

Benign

0.0016

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;.;.;.

MutationTaster

Benign

0.089

P;P

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.53

N;N;N;N

REVEL

Benign

0.048

Sift

Benign

0.25

T;T;T;T

Sift4G

Benign

0.15

T;.;T;.

Polyphen

0.051

B;.;.;.

Vest4

0.022

MPC

0.20

ClinPred

0.014

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.030

gMVP

0.55

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