Variant 12-120516644-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_032314.4(COQ5):c.497G>A(p.Arg166His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000359 in 1,614,190 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

COQ5
NM_032314.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.714

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03301677).

BP6

Variant 12-120516644-C-T is Benign according to our data. Variant chr12-120516644-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2522235.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COQ5	NM_032314.4 linkuse as main transcript	c.497G>A	p.Arg166His	missense_variant	3/7	ENST00000288532.11	NP_115690.3
COQ5	XM_006719639.3 linkuse as main transcript	c.254G>A	p.Arg85His	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.497G>A	p.Arg166His	missense_variant	3/7	1	NM_032314.4	ENSP00000288532	P1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000517

AC:

AN:

251496

Hom.:

AF XY:

0.0000662

AC XY:

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000342

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000243

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000378

ExAC

AF:

0.0000576

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 27, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.48

CADD

Benign

0.0060

DANN

Benign

0.42

DEOGEN2

Benign

0.040

T;T;T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.031

LIST_S2

Uncertain

0.89

D;D;D;T

M_CAP

Benign

0.0054

MetaRNN

Benign

0.033

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.015

N;.;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.19

PROVEAN

Benign

2.0

N;N;N;N

REVEL

Benign

0.11

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

0.84

T;.;T;.

Polyphen

0.0

B;.;.;.

Vest4

0.028

MutPred

0.50

Loss of MoRF binding (P = 0.0443);.;.;.;

MVP

0.34

MPC

0.19

ClinPred

0.013

GERP RS

-11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.012

gMVP

0.52

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