NM_015679.3:c.60G>T

Variant names:

• chr9-128322349-C-A
• rs11539570
• NM_015679.3:c.60G>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BS1 BS2

The NM_015679.3(TRUB2):​c.60G>T​(p.Gly20Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.015 in 1,614,160 control chromosomes in the GnomAD database, including 216 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G20G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0091 (5 hom., cov: 33)
  • Exomes 𝑓: 0.016 (211 hom.)
• Consequence: TRUB2 NM_015679.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.334
• Publications: 8 publications found

Genes affected

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]

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]

COQ4 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP7: Synonymous conserved (PhyloP=-0.334 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00913 (1390/152280) while in subpopulation SAS AF = 0.0189 (91/4820). AF 95% confidence interval is 0.0157. There are 5 homozygotes in GnomAd4. There are 627 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_015679.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRUB2	NM_015679.3	MANE Select	c.60G>T	p.Gly20Gly	synonymous	Exon 1 of 8	NP_056494.1
	TRUB2	NM_001329861.2		c.60G>T	p.Gly20Gly	synonymous	Exon 1 of 7	NP_001316790.1
	TRUB2	NM_001329863.2		c.-328G>T		5_prime_UTR	Exon 1 of 9	NP_001316792.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRUB2	ENST00000372890.6	TSL:1 MANE Select	c.60G>T	p.Gly20Gly	synonymous	Exon 1 of 8	ENSP00000361982.4
	TRUB2	ENST00000460320.1	TSL:2	n.65G>T		non_coding_transcript_exon	Exon 1 of 9
	COQ4	ENST00000608951.5	TSL:2	c.-510C>A		upstream_gene	N/A	ENSP00000476323.1

Frequencies

GnomAD3 genomes AF: 0.00915 AC: 1393 AN: 152162 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.00246

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00727

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0191

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0148

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.0119 AC: 2990 AN: 251458 AF XY: 0.0131

Gnomad AFR exome AF: 0.00295

Gnomad AMR exome AF: 0.00792

Gnomad ASJ exome AF: 0.0115

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00134

Gnomad NFE exome AF: 0.0158

Gnomad OTH exome AF: 0.0161

GnomAD4 exome AF: 0.0156 AC: 22876 AN: 1461880 Hom.: 211 Cov.: 31 AF XY: 0.0159 AC XY: 11568 AN XY: 727240

African (AFR) AF: 0.00227 AC: 76 AN: 33480

American (AMR) AF: 0.00825 AC: 369 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0113 AC: 296 AN: 26136

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39700

South Asian (SAS) AF: 0.0208 AC: 1792 AN: 86256

European-Finnish (FIN) AF: 0.00168 AC: 90 AN: 53420

Middle Eastern (MID) AF: 0.0186 AC: 107 AN: 5768

European-Non Finnish (NFE) AF: 0.0173 AC: 19247 AN: 1112006

Other (OTH) AF: 0.0148 AC: 895 AN: 60390

GnomAD4 genome AF: 0.00913 AC: 1390 AN: 152280 Hom.: 5 Cov.: 33 AF XY: 0.00842 AC XY: 627 AN XY: 74448

African (AFR) AF: 0.00245 AC: 102 AN: 41550

American (AMR) AF: 0.00726 AC: 111 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3472

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

South Asian (SAS) AF: 0.0189 AC: 91 AN: 4820

European-Finnish (FIN) AF: 0.00141 AC: 15 AN: 10620

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0148 AC: 1007 AN: 68024

Other (OTH) AF: 0.0104 AC: 22 AN: 2114

Alfa AF: 0.00343 Hom.: 5

Bravo AF: 0.00978

EpiCase AF: 0.0159

EpiControl AF: 0.0146

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	9.4
DANN	Benign	0.97
PhyloP100		-0.33
PromoterAI		0.0064	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=100/0	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: rs11539570; hg19: chr9-131084628;