16-57447533-C-A

Variant names:

• chr16-57447533-C-A
• rs766594141
• NM_020312.4:c.28C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020312.4(COQ9):​c.28C>A​(p.Leu10Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000864 in 1,157,234 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. 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. L10F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 8.6e-7 (0 hom.)
• Consequence: COQ9 NM_020312.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.749
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.116000384).

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.28C>A	p.Leu10Ile	missense	Exon 1 of 9	NP_064708.1	O75208-1
	CIAPIN1	NM_020313.4	MANE Select	c.-247G>T		upstream_gene	N/A	NP_064709.2	Q6FI81-1
	CIAPIN1	NM_001308347.2		c.-247G>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.28C>A	p.Leu10Ile	missense	Exon 1 of 9	ENSP00000262507.5	O75208-1
	COQ9	ENST00000895095.1		c.28C>A	p.Leu10Ile	missense	Exon 1 of 10	ENSP00000565154.1
	COQ9	ENST00000895096.1		c.28C>A	p.Leu10Ile	missense	Exon 1 of 9	ENSP00000565155.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 8.64e-7 AC: 1 AN: 1157234 Hom.: 0 Cov.: 32 AF XY: 0.00000179 AC XY: 1 AN XY: 558268

African (AFR) AF: 0.00 AC: 0 AN: 23932

American (AMR) AF: 0.00 AC: 0 AN: 13568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16302

East Asian (EAS) AF: 0.00 AC: 0 AN: 27632

South Asian (SAS) AF: 0.00 AC: 0 AN: 35574

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34528

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4014

European-Non Finnish (NFE) AF: 0.00000105 AC: 1 AN: 955528

Other (OTH) AF: 0.00 AC: 0 AN: 46156

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	6.8
DANN	Benign	0.90
DEOGEN2	Benign	0.0095	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0039	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		-0.75
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.069
Sift	Benign	0.084	T
Sift4G	Benign	0.22	T
Polyphen		0.0010	B
Vest4		0.21
MutPred		0.24		Gain of catalytic residue at L10 (P = 0.0349)
MVP		0.13
MPC		0.17
ClinPred		0.11	T
GERP RS		-7.2
PromoterAI		-0.12	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.051
gMVP		0.28

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: rs766594141; hg19: chr16-57481445;