NM_020312.4:c.37G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6

The NM_020312.4(COQ9):​c.37G>A​(p.Ala13Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000214 in 1,308,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A13G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

COQ9
NM_020312.4 missense

Scores

2
17

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 0.453

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]
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.14311147).
BP6
Variant 16-57447542-G-A is Benign according to our data. Variant chr16-57447542-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1369063. Variant chr16-57447542-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1369063. Variant chr16-57447542-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1369063. Variant chr16-57447542-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1369063. Variant chr16-57447542-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1369063. Variant chr16-57447542-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1369063. Variant chr16-57447542-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1369063. Variant chr16-57447542-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1369063. Variant chr16-57447542-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1369063. Variant chr16-57447542-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1369063. Variant chr16-57447542-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1369063. Variant chr16-57447542-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1369063. Variant chr16-57447542-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1369063. Variant chr16-57447542-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1369063. Variant chr16-57447542-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1369063.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COQ9NM_020312.4 linkc.37G>A p.Ala13Thr missense_variant Exon 1 of 9 ENST00000262507.11 NP_064708.1 O75208-1A0A024R6U3
CIAPIN1NM_020313.4 linkc.-256C>T upstream_gene_variant ENST00000394391.9 NP_064709.2 Q6FI81-1
CIAPIN1NM_001308347.2 linkc.-256C>T upstream_gene_variant NP_001295276.1 Q6FI81-3
CIAPIN1NM_001308358.2 linkc.-256C>T upstream_gene_variant NP_001295287.1 Q6FI81H3BT65

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COQ9ENST00000262507.11 linkc.37G>A p.Ala13Thr missense_variant Exon 1 of 9 1 NM_020312.4 ENSP00000262507.5 O75208-1
CIAPIN1ENST00000394391.9 linkc.-256C>T upstream_gene_variant 1 NM_020313.4 ENSP00000377914.4 Q6FI81-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152244
Hom.:
0
Cov.:
34
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:
0.00316
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000195
AC:
1
AN:
51266
AF XY:
0.00
show subpopulations
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:
0.0000398
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000216
AC:
25
AN:
1156388
Hom.:
0
Cov.:
31
AF XY:
0.0000215
AC XY:
12
AN XY:
557570
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
23998
American (AMR)
AF:
0.0000728
AC:
1
AN:
13738
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
16302
East Asian (EAS)
AF:
0.00
AC:
0
AN:
27710
South Asian (SAS)
AF:
0.0000563
AC:
2
AN:
35508
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
34034
Middle Eastern (MID)
AF:
0.000515
AC:
2
AN:
3880
European-Non Finnish (NFE)
AF:
0.0000168
AC:
16
AN:
955074
Other (OTH)
AF:
0.0000867
AC:
4
AN:
46144
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.481
Heterozygous variant carriers
0
2
4
6
8
10
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
3
AN:
152358
Hom.:
0
Cov.:
34
AF XY:
0.0000268
AC XY:
2
AN XY:
74504
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41596
American (AMR)
AF:
0.00
AC:
0
AN:
15312
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5166
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10630
Middle Eastern (MID)
AF:
0.00340
AC:
1
AN:
294
European-Non Finnish (NFE)
AF:
0.0000294
AC:
2
AN:
68028
Other (OTH)
AF:
0.00
AC:
0
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.542
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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.:
0
Bravo
AF:
0.0000302
ExAC
AF:
0.0000179
AC:
2

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Mar 07, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.37G>A (p.A13T) alteration is located in exon 1 (coding exon 1) of the COQ9 gene. This alteration results from a G to A substitution at nucleotide position 37, causing the alanine (A) at amino acid position 13 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided Uncertain:1
Mar 11, 2022
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 13 of the COQ9 protein (p.Ala13Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with COQ9-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Encephalopathy-hypertrophic cardiomyopathy-renal tubular disease syndrome Benign:1
Sep 20, 2024
3billion
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The homozygous variant was found in patients diagnosed with another variant in a different gene, with no symptoms related to the gene containing the homozygous variant. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
16
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0024
T;T;T;T;.
Eigen
Benign
-0.41
Eigen_PC
Benign
-0.37
FATHMM_MKL
Benign
0.015
N
LIST_S2
Benign
0.68
T;T;T;T;T
M_CAP
Benign
0.036
D
MetaRNN
Benign
0.14
T;T;T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
1.7
L;.;.;.;.
PhyloP100
0.45
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-0.64
N;N;N;N;N
REVEL
Benign
0.052
Sift
Benign
0.13
T;T;D;T;T
Sift4G
Benign
0.082
T;T;T;T;T
Polyphen
0.0
B;.;.;.;.
Vest4
0.22
MVP
0.22
MPC
0.15
ClinPred
0.091
T
GERP RS
2.3
PromoterAI
0.054
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.041
gMVP
0.42
Mutation Taster
=91/9
polymorphism

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

Other links and lift over

dbSNP: rs758943543; hg19: chr16-57481454; API