Genetic Variant COQ10A:p.Pro35Ser (chr12-56267221-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144576.4(COQ10A):c.103C>T(p.Pro35Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,471,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

COQ10A
NM_144576.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.35

Publications

1 publications found

Variant links:

Genes affected

COQ10A (HGNC:26515): (coenzyme Q10A) Predicted to enable ubiquinone binding activity. Predicted to be involved in cellular respiration and ubiquinone biosynthetic process. Predicted to be located in mitochondrial inner membrane. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

COQ10A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.097581625).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144576.4. 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
	COQ10A	NM_144576.4	MANE Select	c.103C>T	p.Pro35Ser	missense	Exon 1 of 5	NP_653177.3
	COQ10A	NM_001099337.2		c.-175C>T		upstream_gene	N/A	NP_001092807.1	Q96MF6-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COQ10A	ENST00000308197.10	TSL:1 MANE Select	c.103C>T	p.Pro35Ser	missense	Exon 1 of 5	ENSP00000312587.5	Q96MF6-1
COQ10A	ENST00000925657.1		c.103C>T	p.Pro35Ser	missense	Exon 1 of 5	ENSP00000595716.1
COQ10A	ENST00000925658.1		c.103C>T	p.Pro35Ser	missense	Exon 1 of 5	ENSP00000595717.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

107602

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000288

AC:

AN:

1319808

Hom.:

Cov.:

AF XY:

0.0000216

AC XY:

AN XY:

647206

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27464

American (AMR)

AF:

0.00

AC:

AN:

24108

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19556

East Asian (EAS)

AF:

0.00

AC:

AN:

32986

South Asian (SAS)

AF:

0.00

AC:

AN:

68462

European-Finnish (FIN)

AF:

0.0000241

AC:

AN:

41564

Middle Eastern (MID)

AF:

0.000209

AC:

AN:

4776

European-Non Finnish (NFE)

AF:

0.0000325

AC:

AN:

1046648

Other (OTH)

AF:

0.0000369

AC:

AN:

54244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152060

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41416

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10574

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

67974

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

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:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0066

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.36

M_CAP

Benign

0.030

MetaRNN

Benign

0.098

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

PhyloP100

1.4

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.13

REVEL

Benign

0.046

Sift

Benign

0.12

Sift4G

Benign

0.82

Polyphen

0.079

Vest4

0.25

MutPred

0.26

Gain of phosphorylation at P35 (P = 0.0073)

MVP

0.30

MPC

0.27

ClinPred

0.16

GERP RS

4.1

PromoterAI

0.12

Neutral

(source)

Varity_R

0.039

gMVP

0.36

Mutation Taster

=95/5

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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