rs76508383

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_020312.4(COQ9):c.835G>A(p.Asp279Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00377 in 1,614,212 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0039 ( 16 hom. )

Consequence

COQ9
NM_020312.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:8

Conservation

PhyloP100: 8.19

Publications

7 publications found

Variant links:

Genes affected

COQ9 (HGNC:25302): (coenzyme Q9) This locus represents a mitochondrial ubiquinone biosynthesis gene. The encoded protein is likely necessary for biosynthesis of coenzyme Q10, as mutations at this locus have been associated with autosomal-recessive neonatal-onset primary coenzyme Q10 deficiency.[provided by RefSeq, Sep 2010]

COQ9 Gene-Disease associations (from GenCC):

encephalopathy-hypertrophic cardiomyopathy-renal tubular disease syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
mitochondrial disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Leigh syndrome
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

COQ9 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_020312.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01204294).

BP6

Variant 16-57459688-G-A is Benign according to our data. Variant chr16-57459688-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 214243.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0027 (412/152328) while in subpopulation NFE AF = 0.00425 (289/68030). AF 95% confidence interval is 0.00385. There are 0 homozygotes in GnomAd4. There are 192 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 16 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020312.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COQ9	NM_020312.4	MANE Select	c.835G>A	p.Asp279Asn	missense	Exon 7 of 9	NP_064708.1	O75208-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COQ9	ENST00000262507.11	TSL:1 MANE Select	c.835G>A	p.Asp279Asn	missense	Exon 7 of 9	ENSP00000262507.5	O75208-1
COQ9	ENST00000895095.1		c.1039G>A	p.Asp347Asn	missense	Exon 8 of 10	ENSP00000565154.1
COQ9	ENST00000895096.1		c.835G>A	p.Asp279Asn	missense	Exon 7 of 9	ENSP00000565155.1

Frequencies

GnomAD3 genomes

AF:

0.00271

AC:

413

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00294

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00329

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00425

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.00233

AC:

587

AN:

251460

AF XY:

0.00242

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.00119

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00296

Gnomad NFE exome

AF:

0.00389

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00388

AC:

5675

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00377

AC XY:

2743

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.000597

AC:

AN:

33480

American (AMR)

AF:

0.00110

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000153

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000243

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00266

AC:

142

AN:

53420

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00472

AC:

5254

AN:

1112006

Other (OTH)

AF:

0.00305

AC:

184

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

317

633

950

1266

1583

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

194

388

582

776

970

<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:

0.00270

AC:

412

AN:

152328

Hom.:

Cov.:

AF XY:

0.00258

AC XY:

192

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.000962

AC:

AN:

41568

American (AMR)

AF:

0.00288

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00329

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00425

AC:

289

AN:

68030

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

115

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00362

Hom.:

Bravo

AF:

0.00258

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00431

EpiControl

AF:

0.00427

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (7)

COQ9-related disorder (1)

Encephalopathy-hypertrophic cardiomyopathy-renal tubular disease syndrome (1)

Leigh syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0091

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.4

PhyloP100

8.2

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-4.3

REVEL

Benign

0.20

Sift

Uncertain

0.0020

Sift4G

Benign

0.087

Varity_R

0.87

gMVP

0.81

Mutation Taster

=84/16

polymorphism

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over