16-57447481-C-G

Variant names:

• chr16-57447481-C-G
• rs547268811
• NM_020312.4:c.-25C>G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Moderate BS1_Supporting BS2

The NM_020312.4(COQ9):​c.-25C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000618 in 1,281,412 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (2 hom., cov: 34)
  • Exomes 𝑓: 0.00054 (2 hom.)
• Consequence: COQ9 NM_020312.4 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.02
• Publications: 1 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0012 (183/152320) while in subpopulation EAS AF = 0.00174 (9/5166). AF 95% confidence interval is 0.000909. There are 2 homozygotes in GnomAd4. There are 134 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.-25C>G		5_prime_UTR	Exon 1 of 9	NP_064708.1	O75208-1
	CIAPIN1	NM_020313.4	MANE Select	c.-195G>C		upstream_gene	N/A	NP_064709.2	Q6FI81-1
	CIAPIN1	NM_001308347.2		c.-195G>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.-25C>G		5_prime_UTR	Exon 1 of 9	ENSP00000262507.5	O75208-1
	COQ9	ENST00000960665.1		c.-25C>G		5_prime_UTR	Exon 1 of 9	ENSP00000630724.1
	COQ9	ENST00000960667.1		c.-25C>G		5_prime_UTR	Exon 1 of 8	ENSP00000630726.1

Frequencies

GnomAD3 genomes AF: 0.00120 AC: 183 AN: 152202 Hom.: 2 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0133

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00532 AC: 124 AN: 23292 AF XY: 0.00514

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00192

Gnomad FIN exome AF: 0.0160

Gnomad NFE exome AF: 0.000744

Gnomad OTH exome AF: 0.00248

GnomAD4 exome AF: 0.000539 AC: 609 AN: 1129092 Hom.: 2 Cov.: 32 AF XY: 0.000555 AC XY: 300 AN XY: 540684

African (AFR) AF: 0.00 AC: 0 AN: 23340

American (AMR) AF: 0.00 AC: 0 AN: 10140

Ashkenazi Jewish (ASJ) AF: 0.000264 AC: 4 AN: 15156

East Asian (EAS) AF: 0.00274 AC: 74 AN: 26966

South Asian (SAS) AF: 0.0000656 AC: 2 AN: 30470

European-Finnish (FIN) AF: 0.0128 AC: 433 AN: 33926

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4396

European-Non Finnish (NFE) AF: 0.0000798 AC: 75 AN: 939622

Other (OTH) AF: 0.000466 AC: 21 AN: 45076

GnomAD4 genome AF: 0.00120 AC: 183 AN: 152320 Hom.: 2 Cov.: 34 AF XY: 0.00180 AC XY: 134 AN XY: 74486

African (AFR) AF: 0.00 AC: 0 AN: 41588

American (AMR) AF: 0.00 AC: 0 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.0133 AC: 141 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 68014

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.000636 Hom.: 0

Bravo AF: 0.000189

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Encephalopathy-hypertrophic cardiomyopathy-renal tubular disease syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	5.4
DANN	Benign	0.62
PhyloP100		-1.0
PromoterAI		-0.039	Neutral
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs547268811; hg19: chr16-57481393;