16-57447522-T-G

Variant names:

• chr16-57447522-T-G
• rs1418552732
• NM_020312.4:c.17T>G

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.17T>G​(p.Val6Gly) 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. 13/21 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. V6A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000028 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: COQ9 NM_020312.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.811
• 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=0.13899782).

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.17T>G	p.Val6Gly	missense	Exon 1 of 9	NP_064708.1	O75208-1
	CIAPIN1	NM_020313.4	MANE Select	c.-236A>C		upstream_gene	N/A	NP_064709.2	Q6FI81-1
	CIAPIN1	NM_001308347.2		c.-236A>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.17T>G	p.Val6Gly	missense	Exon 1 of 9	ENSP00000262507.5	O75208-1
	COQ9	ENST00000895095.1		c.17T>G	p.Val6Gly	missense	Exon 1 of 10	ENSP00000565154.1
	COQ9	ENST00000895096.1		c.17T>G	p.Val6Gly	missense	Exon 1 of 9	ENSP00000565155.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000279 AC: 3 AN: 1076134 Hom.: 0 Cov.: 32 AF XY: 0.00000193 AC XY: 1 AN XY: 518900

⚠️ 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: 20850

American (AMR) AF: 0.00 AC: 0 AN: 10520

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12578

East Asian (EAS) AF: 0.00 AC: 0 AN: 21376

South Asian (SAS) AF: 0.00 AC: 0 AN: 34244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26012

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3324

European-Non Finnish (NFE) AF: 0.00000220 AC: 2 AN: 907064

Other (OTH) AF: 0.0000249 AC: 1 AN: 40166

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000222209), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 34

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	0.069
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	18
DANN	Benign	0.82
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.0085	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.81
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.23
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.025	D
Polyphen		0.0	B
Vest4		0.41
MutPred		0.52		Gain of loop (P = 0.0013)
MVP		0.19
MPC		0.21
ClinPred		0.37	T
GERP RS		3.0
PromoterAI		-0.054	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.38
gMVP		0.47

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: rs1418552732; hg19: chr16-57481434;