9-128322834-C-T

Variant names:

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

Variant summary

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

The ENST00000608951.5(COQ4):​c.-25C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0032 in 1,528,794 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0045 (7 hom., cov: 33)
  • Exomes 𝑓: 0.0031 (87 hom.)
• Consequence: COQ4 ENST00000608951.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 9-128322834-C-T is Benign according to our data. Variant chr9-128322834-C-T is described in ClinVar as Benign. ClinVar VariationId is 381170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00448 (682/152384) while in subpopulation SAS AF = 0.0352 (170/4832). AF 95% confidence interval is 0.0309. There are 7 homozygotes in GnomAd4. There are 377 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

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>T		upstream_gene	N/A	NP_057119.3	Q9Y3A0-1
	COQ4	NM_001305942.2		c.-25C>T		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>T		5_prime_UTR	Exon 1 of 8	ENSP00000596165.1
	COQ4	ENST00000926105.1		c.-25C>T		5_prime_UTR	Exon 1 of 8	ENSP00000596164.1
	COQ4	ENST00000608951.5	TSL:2	c.-25C>T		5_prime_UTR	Exon 1 of 3	ENSP00000476323.1	V9GY32

Frequencies

GnomAD3 genomes AF: 0.00451 AC: 686 AN: 152266 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.00817

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00471

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0354

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00116

Gnomad OTH AF: 0.00764

GnomAD2 exomes AF: 0.00763 AC: 1018 AN: 133402 AF XY: 0.00916

Gnomad AFR exome AF: 0.00927

Gnomad AMR exome AF: 0.00565

Gnomad ASJ exome AF: 0.000276

Gnomad EAS exome AF: 0.000198

Gnomad FIN exome AF: 0.000214

Gnomad NFE exome AF: 0.000855

Gnomad OTH exome AF: 0.00843

GnomAD4 exome AF: 0.00306 AC: 4208 AN: 1376410 Hom.: 87 Cov.: 30 AF XY: 0.00400 AC XY: 2712 AN XY: 678726

African (AFR) AF: 0.00936 AC: 288 AN: 30770

American (AMR) AF: 0.00564 AC: 179 AN: 31714

Ashkenazi Jewish (ASJ) AF: 0.000495 AC: 12 AN: 24246

East Asian (EAS) AF: 0.0000846 AC: 3 AN: 35476

South Asian (SAS) AF: 0.0326 AC: 2554 AN: 78294

European-Finnish (FIN) AF: 0.000223 AC: 9 AN: 40402

Middle Eastern (MID) AF: 0.00640 AC: 36 AN: 5624

European-Non Finnish (NFE) AF: 0.000772 AC: 828 AN: 1072754

Other (OTH) AF: 0.00523 AC: 299 AN: 57130

GnomAD4 genome AF: 0.00448 AC: 682 AN: 152384 Hom.: 7 Cov.: 33 AF XY: 0.00506 AC XY: 377 AN XY: 74514

African (AFR) AF: 0.00808 AC: 336 AN: 41600

American (AMR) AF: 0.00470 AC: 72 AN: 15308

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

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

South Asian (SAS) AF: 0.0352 AC: 170 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00116 AC: 79 AN: 68044

Other (OTH) AF: 0.00756 AC: 16 AN: 2116

Alfa AF: 0.00269 Hom.: 1

Bravo AF: 0.00430

Asia WGS AF: 0.0180 AC: 63 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.3
DANN	Benign	0.87
PhyloP100		0.0070
PromoterAI		-0.11	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: rs144235048; hg19: chr9-131085113;