Variant 12-120522252-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_032314.4(COQ5):c.314T>C(p.Leu105Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000182 in 1,614,164 control chromosomes in the GnomAD database, including 4 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 4 hom. )

Consequence

COQ5
NM_032314.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.90

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008389771).

BP6

Variant 12-120522252-A-G is Benign according to our data. Variant chr12-120522252-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2672526.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COQ5	NM_032314.4 linkuse as main transcript	c.314T>C	p.Leu105Pro	missense_variant	2/7	ENST00000288532.11	NP_115690.3
COQ5	XM_006719639.3 linkuse as main transcript	c.71T>C	p.Leu24Pro	missense_variant	3/8		XP_006719702.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COQ5	ENST00000288532.11 linkuse as main transcript	c.314T>C	p.Leu105Pro	missense_variant	2/7	1	NM_032314.4	ENSP00000288532	P1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000441

AC:

111

AN:

251450

Hom.:

AF XY:

0.000589

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00349

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000193

AC:

282

AN:

1461882

Hom.:

Cov.:

AF XY:

0.000274

AC XY:

199

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00300

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152282

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000831

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.000585

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2023

COQ5: BP4, BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.056

T;T;T;T;.

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.099

LIST_S2

Benign

0.79

T;T;T;T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.0084

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.14

N;.;.;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.4

N;N;N;N;N

REVEL

Benign

0.17

Sift

Benign

0.20

T;T;T;T;T

Sift4G

Benign

0.21

T;T;.;.;.

Polyphen

0.0

B;B;.;.;.

Vest4

0.31

MutPred

0.53

Gain of catalytic residue at P104 (P = 0.0119);Gain of catalytic residue at P104 (P = 0.0119);.;.;.;

MVP

0.40

MPC

0.24

ClinPred

0.035

GERP RS

4.7

Varity_R

0.15

gMVP

0.72

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