NM_024876.4:c.1055C>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_024876.4(COQ8B):c.1055C>G(p.Thr352Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0429 in 1,614,150 control chromosomes in the GnomAD database, including 1,759 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T352T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.032 ( 120 hom., cov: 33)

Exomes 𝑓: 0.044 ( 1639 hom. )

Consequence

COQ8B
NM_024876.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.242

Publications

14 publications found

Variant links:

Genes affected

COQ8B (HGNC:19041): (coenzyme Q8B) This gene encodes a protein with two copies of a domain found in protein kinases. The encoded protein has a complete protein kinase catalytic domain, and a truncated domain that contains only the active and binding sites of the protein kinase domain, however, it is not known whether the protein has any kinase activity. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

COQ8B Gene-Disease associations (from GenCC):

mitochondrial disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
nephrotic syndrome, type 9
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
familial idiopathic steroid-resistant nephrotic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

COQ8B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033581555).

BP6

Variant 19-40700155-G-C is Benign according to our data. Variant chr19-40700155-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 380101.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0321 (4886/152324) while in subpopulation NFE AF = 0.0478 (3249/68030). AF 95% confidence interval is 0.0464. There are 120 homozygotes in GnomAd4. There are 2377 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 120 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COQ8B	NM_024876.4 link	c.1055C>G	p.Thr352Arg	missense_variant	Exon 12 of 15	ENST00000324464.8	NP_079152.3
COQ8B	NM_001142555.3 link	c.932C>G	p.Thr311Arg	missense_variant	Exon 11 of 14		NP_001136027.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COQ8B	ENST00000324464.8 link	c.1055C>G	p.Thr352Arg	missense_variant	Exon 12 of 15	1	NM_024876.4	ENSP00000315118.3

Frequencies

GnomAD3 genomes

AF:

0.0321

AC:

4888

AN:

152206

Hom.:

120

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00827

Gnomad AMI

AF:

0.0647

Gnomad AMR

AF:

0.0235

Gnomad ASJ

AF:

0.0665

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00518

Gnomad FIN

AF:

0.0496

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0478

Gnomad OTH

AF:

0.0387

GnomAD2 exomes

AF:

0.0336

AC:

8440

AN:

251352

AF XY:

0.0338

show subpopulations

Gnomad AFR exome

AF:

0.00647

Gnomad AMR exome

AF:

0.0177

Gnomad ASJ exome

AF:

0.0654

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0491

Gnomad NFE exome

AF:

0.0492

Gnomad OTH exome

AF:

0.0419

GnomAD4 exome

AF:

0.0440

AC:

64352

AN:

1461826

Hom.:

1639

Cov.:

AF XY:

0.0426

AC XY:

30982

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.00726

AC:

243

AN:

33478

American (AMR)

AF:

0.0193

AC:

861

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0648

AC:

1694

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.00550

AC:

474

AN:

86256

European-Finnish (FIN)

AF:

0.0501

AC:

2677

AN:

53418

Middle Eastern (MID)

AF:

0.0515

AC:

297

AN:

5768

European-Non Finnish (NFE)

AF:

0.0500

AC:

55636

AN:

1111952

Other (OTH)

AF:

0.0409

AC:

2468

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

3258

6515

9773

13030

16288

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2062

4124

6186

8248

10310

<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:

0.0321

AC:

4886

AN:

152324

Hom.:

120

Cov.:

AF XY:

0.0319

AC XY:

2377

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.00825

AC:

343

AN:

41582

American (AMR)

AF:

0.0235

AC:

359

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0665

AC:

231

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.00518

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0496

AC:

526

AN:

10614

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0478

AC:

3249

AN:

68030

Other (OTH)

AF:

0.0383

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

255

509

764

1018

1273

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<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:

0.0262

Hom.:

Bravo

AF:

0.0306

TwinsUK

AF:

0.0429

AC:

159

ALSPAC

AF:

0.0483

AC:

186

ESP6500AA

AF:

0.00794

AC:

ESP6500EA

AF:

0.0533

AC:

458

ExAC

AF:

0.0334

AC:

4054

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.0534

EpiControl

AF:

0.0506

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Feb 23, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

not specified

Benign:1

Jan 25, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Kidney disorder

Benign:1

Apr 01, 2019

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.038

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.20

(source)

DANN

Benign

0.34

DEOGEN2

Benign

0.0037

T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.63

T;T

MetaRNN

Benign

0.0034

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;.

PhyloP100

0.24

PrimateAI

Benign

0.33

PROVEAN

Benign

1.1

N;N

REVEL

Benign

0.16

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Vest4

0.076

ClinPred

0.000020

GERP RS

1.4

Varity_R

0.047

gMVP

0.65

Mutation Taster

=98/2

polymorphism (auto)

(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

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