9-128322839-C-G

Variant names:

• chr9-128322839-C-G
• rs372363685
• NM_016035.5:c.-20C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_016035.5(COQ4):​c.-20C>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 0.00078 in 1,534,228 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0041 (5 hom., cov: 33)
  • Exomes 𝑓: 0.00041 (4 hom.)
• Consequence: COQ4 NM_016035.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.56
• Publications: 1 publications found

Genes affected

COQ4 (HGNC:19693): (coenzyme Q4) This gene encodes a component of the coenzyme Q biosynthesis pathway. Coenzyme Q, an essential component of the electron transport chain, shuttles electrons between complexes I or II to complex III of the mitochondrial transport chain. This protein appears to play a structural role in stabilizing a complex that contains most of the coenzyme Q biosynthesis enzymes. Mutations in this gene are associated with mitochondrial disorders linked to coenzyme Q deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

TRUB2 (HGNC:17170): (TruB pseudouridine synthase family member 2) Pseudouridine is an abundant component of rRNAs and tRNAs and is enzymatically generated by isomerization of uridine by pseudouridine synthase (Zucchini et al., 2003 [PubMed 12736709]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 9-128322839-C-G is Benign according to our data. Variant chr9-128322839-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 385011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00409 (624/152382) while in subpopulation AFR AF = 0.0145 (604/41600). AF 95% confidence interval is 0.0136. There are 5 homozygotes in GnomAd4. There are 305 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016035.5. 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
	COQ4	NM_016035.5	MANE Select	c.-20C>G		5_prime_UTR	Exon 1 of 7	NP_057119.3	Q9Y3A0-1
	COQ4	NM_001305942.2		c.-20C>G		5_prime_UTR	Exon 1 of 4	NP_001292871.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COQ4	ENST00000300452.8	TSL:1 MANE Select	c.-20C>G		5_prime_UTR	Exon 1 of 7	ENSP00000300452.3	Q9Y3A0-1
	COQ4	ENST00000926106.1		c.-20C>G		5_prime_UTR	Exon 1 of 8	ENSP00000596165.1
	COQ4	ENST00000926105.1		c.-20C>G		5_prime_UTR	Exon 1 of 8	ENSP00000596164.1

Frequencies

GnomAD3 genomes AF: 0.00409 AC: 623 AN: 152264 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.0145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000981

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000959 AC: 133 AN: 138646 AF XY: 0.000785

Gnomad AFR exome AF: 0.0161

Gnomad AMR exome AF: 0.000414

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000960

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000249

GnomAD4 exome AF: 0.000414 AC: 572 AN: 1381846 Hom.: 4 Cov.: 30 AF XY: 0.000372 AC XY: 254 AN XY: 681890

African (AFR) AF: 0.0167 AC: 518 AN: 30960

American (AMR) AF: 0.000400 AC: 13 AN: 32520

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24480

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35656

South Asian (SAS) AF: 0.00 AC: 0 AN: 79146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40826

Middle Eastern (MID) AF: 0.000355 AC: 2 AN: 5638

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1075316

Other (OTH) AF: 0.000663 AC: 38 AN: 57304

GnomAD4 genome AF: 0.00409 AC: 624 AN: 152382 Hom.: 5 Cov.: 33 AF XY: 0.00409 AC XY: 305 AN XY: 74522

African (AFR) AF: 0.0145 AC: 604 AN: 41600

American (AMR) AF: 0.000980 AC: 15 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68034

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.000386 Hom.: 0

Bravo AF: 0.00490

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.9
DANN	Benign	0.78
PhyloP100		-1.6
PromoterAI		-0.048	Neutral
Mutation Taster		=300/0	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: rs372363685; hg19: chr9-131085118;