16-57447510-C-G

Variant names:

• chr16-57447510-C-G
• rs2030147526
• NM_020312.4:c.5C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020312.4(COQ9):​c.5C>G​(p.Ala2Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000154 in 1,301,250 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 34)
  • Exomes 𝑓: 8.7e-7 (0 hom.)
• Consequence: COQ9 NM_020312.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.61
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38572016).

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.5C>G	p.Ala2Gly	missense	Exon 1 of 9	NP_064708.1	O75208-1
	CIAPIN1	NM_020313.4	MANE Select	c.-224G>C		upstream_gene	N/A	NP_064709.2	Q6FI81-1
	CIAPIN1	NM_001308347.2		c.-224G>C		upstream_gene	N/A	NP_001295276.1	Q6FI81-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COQ9	ENST00000262507.11	TSL:1 MANE Select	c.5C>G	p.Ala2Gly	missense	Exon 1 of 9	ENSP00000262507.5	O75208-1
	COQ9	ENST00000895095.1		c.5C>G	p.Ala2Gly	missense	Exon 1 of 10	ENSP00000565154.1
	COQ9	ENST00000895096.1		c.5C>G	p.Ala2Gly	missense	Exon 1 of 9	ENSP00000565155.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152182 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000241

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 8.70e-7 AC: 1 AN: 1149068 Hom.: 0 Cov.: 32 AF XY: 0.00000181 AC XY: 1 AN XY: 553252

African (AFR) AF: 0.00 AC: 0 AN: 23732

American (AMR) AF: 0.00 AC: 0 AN: 12990

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16100

East Asian (EAS) AF: 0.00 AC: 0 AN: 27248

South Asian (SAS) AF: 0.00 AC: 0 AN: 34228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4254

European-Non Finnish (NFE) AF: 0.00000105 AC: 1 AN: 950062

Other (OTH) AF: 0.00 AC: 0 AN: 45868

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152182 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 74346

African (AFR) AF: 0.0000241 AC: 1 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	24
DANN	Uncertain	0.97
DEOGEN2	Benign	0.0027	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.6
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.14
Sift	Benign	0.048	D
Sift4G	Benign	0.067	T
Polyphen		0.88	P
Vest4		0.42
MutPred		0.19		Gain of loop (P = 0.0045)
MVP		0.44
MPC		0.16
ClinPred		0.93	D
GERP RS		5.6
PromoterAI		-0.89	Under-expression
Varity_R		0.16
gMVP		0.26
Mutation Taster		=76/24	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

Other links and lift over

dbSNP: rs2030147526; hg19: chr16-57481422;