rs144235048

Variant names:

• chr9-128322834-C-G
• rs144235048
• ENST00000926106.1:c.-25C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-128322834-C-G
• chr9-128322834-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000608951.5(COQ4):​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 0.00000581 in 1,376,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000058 (0 hom.)
• Consequence: COQ4 ENST00000608951.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000608951.5. 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.-25C>G		upstream_gene	N/A	NP_057119.3	Q9Y3A0-1
	COQ4	NM_001305942.2		c.-25C>G		upstream_gene	N/A	NP_001292871.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COQ4	ENST00000926106.1		c.-25C>G		5_prime_UTR	Exon 1 of 8	ENSP00000596165.1
	COQ4	ENST00000926105.1		c.-25C>G		5_prime_UTR	Exon 1 of 8	ENSP00000596164.1
	COQ4	ENST00000608951.5	TSL:2	c.-25C>G		5_prime_UTR	Exon 1 of 3	ENSP00000476323.1	V9GY32

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000225 AC: 3 AN: 133402 AF XY: 0.0000273

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000581 AC: 8 AN: 1376416 Hom.: 0 Cov.: 30 AF XY: 0.00000884 AC XY: 6 AN XY: 678732

African (AFR) AF: 0.00 AC: 0 AN: 30770

American (AMR) AF: 0.00 AC: 0 AN: 31716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24246

East Asian (EAS) AF: 0.00 AC: 0 AN: 35476

South Asian (SAS) AF: 0.0000894 AC: 7 AN: 78296

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5624

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1072754

Other (OTH) AF: 0.0000175 AC: 1 AN: 57132

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.6
DANN	Benign	0.78
PhyloP100		0.0070
PromoterAI		-0.19	Neutral

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: rs144235048; hg19: chr9-131085113;