rs2030150275

Variant names:

• chr16-57447530-G-C
• rs2030150275
• NM_020312.4:c.25G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-57447530-G-C
• chr16-57447530-G-T
• chr16-57447530-G-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.25G>C​(p.Ala9Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000863 in 1,159,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A9V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000086 (0 hom.)
• Consequence: COQ9 NM_020312.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0260
• 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=0.091993034).

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.25G>C	p.Ala9Pro	missense	Exon 1 of 9	NP_064708.1	O75208-1
	CIAPIN1	NM_020313.4	MANE Select	c.-244C>G		upstream_gene	N/A	NP_064709.2	Q6FI81-1
	CIAPIN1	NM_001308347.2		c.-244C>G		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.25G>C	p.Ala9Pro	missense	Exon 1 of 9	ENSP00000262507.5	O75208-1
	COQ9	ENST00000895095.1		c.25G>C	p.Ala9Pro	missense	Exon 1 of 10	ENSP00000565154.1
	COQ9	ENST00000895096.1		c.25G>C	p.Ala9Pro	missense	Exon 1 of 9	ENSP00000565155.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000863 AC: 10 AN: 1159262 Hom.: 0 Cov.: 32 AF XY: 0.0000125 AC XY: 7 AN XY: 559818

African (AFR) AF: 0.0000836 AC: 2 AN: 23922

American (AMR) AF: 0.00 AC: 0 AN: 13466

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16304

East Asian (EAS) AF: 0.00 AC: 0 AN: 27692

South Asian (SAS) AF: 0.000169 AC: 6 AN: 35574

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34712

Middle Eastern (MID) AF: 0.000243 AC: 1 AN: 4110

European-Non Finnish (NFE) AF: 0.00000104 AC: 1 AN: 957206

Other (OTH) AF: 0.00 AC: 0 AN: 46276

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	14
DANN	Benign	0.87
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.0079	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.026
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.21
Sift	Benign	0.097	T
Sift4G	Benign	0.27	T
Polyphen		0.21	B
Vest4		0.51
MutPred		0.36		Loss of helix (P = 0.0304)
MVP		0.13
MPC		0.21
ClinPred		0.14	T
GERP RS		1.3
PromoterAI		0.032	Neutral
Varity_R		0.11
gMVP		0.50
Mutation Taster		=96/4	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: rs2030150275; hg19: chr16-57481442;