Genetic Variant COQ9:p.Ala5Glu (chr16-57447519-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_020312.4(COQ9):c.14C>A(p.Ala5Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A5G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

COQ9
NM_020312.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.370

Publications

0 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 links:

CIAPIN1 (HGNC:28050): (cytokine induced apoptosis inhibitor 1) CIAPIN1 is a cytokine-induced inhibitor of apoptosis with no relation to apoptosis regulatory molecules of the BCL2 (MIM 151430) or CASP (see MIM 147678) families. Expression of CIAPIN1 is dependent on growth factor stimulation (Shibayama et al., 2004 [PubMed 14970183]).[supplied by OMIM, Mar 2008]

CIAPIN1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COQ9	NM_020312.4	MANE Select	c.14C>A	p.Ala5Glu	missense	Exon 1 of 9	NP_064708.1	O75208-1
CIAPIN1	NM_020313.4	MANE Select	c.-233G>T		upstream_gene	N/A	NP_064709.2	Q6FI81-1
CIAPIN1	NM_001308347.2		c.-233G>T		upstream_gene	N/A	NP_001295276.1	Q6FI81-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COQ9	ENST00000262507.11	TSL:1 MANE Select	c.14C>A	p.Ala5Glu	missense	Exon 1 of 9	ENSP00000262507.5	O75208-1
COQ9	ENST00000895095.1		c.14C>A	p.Ala5Glu	missense	Exon 1 of 10	ENSP00000565154.1
COQ9	ENST00000895096.1		c.14C>A	p.Ala5Glu	missense	Exon 1 of 9	ENSP00000565155.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1153162

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

556008

African (AFR)

AF:

0.00

AC:

AN:

23784

American (AMR)

AF:

0.00

AC:

AN:

13444

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16174

East Asian (EAS)

AF:

0.00

AC:

AN:

27302

South Asian (SAS)

AF:

0.00

AC:

AN:

35132

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34112

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4164

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

953098

Other (OTH)

AF:

0.00

AC:

AN:

45952

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.026

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.0074

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.0077

LIST_S2

Benign

0.74

M_CAP

Benign

0.063

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.2

PhyloP100

-0.37

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.95

REVEL

Benign

0.12

Sift

Uncertain

0.0050

Sift4G

Benign

0.13

Polyphen

0.18

Vest4

0.44

MutPred

0.35

Loss of helix (P = 0.0167)

MVP

0.17

MPC

0.19

ClinPred

0.63

GERP RS

0.74

PromoterAI

0.021

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.13

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.58

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.58

Position offset: 1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over