rs2030147526

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr16-57447510-C-A
• chr16-57447510-C-G
• chr16-57447510-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020312.4(COQ9):​c.5C>A​(p.Ala2Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000087 in 1,149,066 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>A	p.Ala2Glu	missense	Exon 1 of 9	NP_064708.1	O75208-1
	CIAPIN1	NM_020313.4	MANE Select	c.-224G>T		upstream_gene	N/A	NP_064709.2	Q6FI81-1
	CIAPIN1	NM_001308347.2		c.-224G>T		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>A	p.Ala2Glu	missense	Exon 1 of 9	ENSP00000262507.5	O75208-1
	COQ9	ENST00000895095.1		c.5C>A	p.Ala2Glu	missense	Exon 1 of 10	ENSP00000565154.1
	COQ9	ENST00000895096.1		c.5C>A	p.Ala2Glu	missense	Exon 1 of 9	ENSP00000565155.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 8.70e-7 AC: 1 AN: 1149066 Hom.: 0 Cov.: 32 AF XY: 0.00000181 AC XY: 1 AN XY: 553250

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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: 0.0000292 AC: 1 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: 0.00 AC: 0 AN: 950060

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

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0021	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.053	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.6
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.19
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.021	D
Polyphen		0.96	D
Vest4		0.51
MutPred		0.29		Loss of helix (P = 0.0093)
MVP		0.50
MPC		0.19
ClinPred		0.93	D
GERP RS		5.6
PromoterAI		-0.53	Under-expression
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.32
gMVP		0.32

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;