chr9-128323094-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1

The NM_016035.5(COQ4):c.149G>C(p.Gly50Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.999 in 1,611,922 control chromosomes in the GnomAD database, including 804,336 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 Benign (★★).

Frequency

Genomes: 𝑓 1.0 ( 75679 hom., cov: 36)

Exomes 𝑓: 1.0 ( 728657 hom. )

Consequence

COQ4
NM_016035.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0510

Publications

25 publications found

Variant links:

Genes affected

COQ4 (HGNC:19693): (coenzyme Q4) This gene encodes a component of the coenzyme Q biosynthesis pathway. Coenzyme Q, an essential component of the electron transport chain, shuttles electrons between complexes I or II to complex III of the mitochondrial transport chain. This protein appears to play a structural role in stabilizing a complex that contains most of the coenzyme Q biosynthesis enzymes. Mutations in this gene are associated with mitochondrial disorders linked to coenzyme Q deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

COQ4 Gene-Disease associations (from GenCC):

mitochondrial disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet

COQ4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

PM1

In a chain Ubiquinone biosynthesis protein COQ4 homolog, mitochondrial (size 234) in uniprot entity COQ4_HUMAN there are 20 pathogenic changes around while only 7 benign (74%) in NM_016035.5

BP4

Computational evidence support a benign effect (MetaRNN=6.3978564E-7).

BP6

Variant 9-128323094-G-C is Benign according to our data. Variant chr9-128323094-G-C is described in ClinVar as [Benign]. Clinvar id is 1167959.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COQ4	NM_016035.5 link	c.149G>C	p.Gly50Ala	missense_variant	Exon 2 of 7	ENST00000300452.8	NP_057119.3	Q9Y3A0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
COQ4	ENST00000300452.8 link	c.149G>C	p.Gly50Ala	missense_variant	Exon 2 of 7	1	NM_016035.5	ENSP00000300452.3	Q9Y3A0-1
COQ4	ENST00000372875.3 link	c.149G>C	p.Gly50Ala	missense_variant	Exon 2 of 4	2		ENSP00000361966.3	Q5T4B9
COQ4	ENST00000608951.5 link	c.149G>C	p.Gly50Ala	missense_variant	Exon 2 of 3	2		ENSP00000476323.1	V9GY32
COQ4	ENST00000609948.1 link	c.149G>C	p.Gly50Ala	missense_variant	Exon 2 of 2	2		ENSP00000477292.1	V9GZ09

Frequencies

GnomAD3 genomes

AF:

0.997

AC:

151751

AN:

152270

Hom.:

75620

Cov.:

show subpopulations

Gnomad AFR

AF:

0.989

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.997

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.994

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.995

GnomAD2 exomes

AF:

0.999

AC:

238516

AN:

238778

AF XY:

0.999

show subpopulations

Gnomad AFR exome

AF:

0.990

Gnomad AMR exome

AF:

0.998

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.999

Gnomad OTH exome

AF:

0.998

GnomAD4 exome

AF:

0.999

AC:

1458423

AN:

1459534

Hom.:

728657

Cov.:

AF XY:

0.999

AC XY:

725638

AN XY:

726156

show subpopulations

African (AFR)

AF:

0.989

AC:

33080

AN:

33452

American (AMR)

AF:

0.998

AC:

44626

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

26102

AN:

26102

East Asian (EAS)

AF:

1.00

AC:

39672

AN:

39672

South Asian (SAS)

AF:

1.00

AC:

86206

AN:

86218

European-Finnish (FIN)

AF:

1.00

AC:

51592

AN:

51592

Middle Eastern (MID)

AF:

0.996

AC:

5732

AN:

5756

European-Non Finnish (NFE)

AF:

1.00

AC:

1111194

AN:

1111728

Other (OTH)

AF:

0.998

AC:

60219

AN:

60310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

121

181

242

302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21670

43340

65010

86680

108350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.997

AC:

151869

AN:

152388

Hom.:

75679

Cov.:

AF XY:

0.997

AC XY:

74260

AN XY:

74518

show subpopulations

African (AFR)

AF:

0.989

AC:

41154

AN:

41596

American (AMR)

AF:

0.997

AC:

15266

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3472

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5184

AN:

5184

South Asian (SAS)

AF:

1.00

AC:

4831

AN:

4832

European-Finnish (FIN)

AF:

1.00

AC:

10626

AN:

10626

Middle Eastern (MID)

AF:

0.993

AC:

292

AN:

294

European-Non Finnish (NFE)

AF:

1.00

AC:

68026

AN:

68046

Other (OTH)

AF:

0.995

AC:

2106

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

107

134

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

916

1832

2748

3664

4580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.854

Hom.:

19522

Bravo

AF:

0.996

TwinsUK

AF:

1.00

AC:

3708

ALSPAC

AF:

1.00

AC:

3853

ESP6500AA

AF:

0.992

AC:

4180

ESP6500EA

AF:

1.00

AC:

8319

ExAC

AF:

0.999

AC:

119418

Asia WGS

AF:

1.00

AC:

3478

AN:

3478

EpiCase

AF:

1.00

EpiControl

AF:

0.999

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.67

CADD

Benign

7.3

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.070

T;T;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0017

LIST_S2

Benign

0.060

T;T;T;T

MetaRNN

Benign

6.4e-7

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.8

N;.;.;.

PhyloP100

0.051

PrimateAI

Benign

0.31

PROVEAN

Benign

1.9

N;.;.;N

REVEL

Benign

0.018

Sift

Benign

1.0

T;.;.;T

Sift4G

Benign

0.95

T;T;T;T

Polyphen

0.0

B;.;.;B

Vest4

0.032

MPC

0.42

ClinPred

0.00038

GERP RS

-2.6

PromoterAI

-0.041

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.051

gMVP

0.53

Mutation Taster

=67/33

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over