rs11539570

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr9-128322349-C-A
• chr9-128322349-C-T

Variant summary

Our verdict is Benign. Variant got -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.

• 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

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]

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRUB2	NM_015679.3	c.60G>T	p.Gly20Gly	synonymous_variant	Exon 1 of 8	ENST00000372890.6	NP_056494.1
TRUB2	NM_001329861.2	c.60G>T	p.Gly20Gly	synonymous_variant	Exon 1 of 7		NP_001316790.1
TRUB2	NM_001329863.2	c.-328G>T		5_prime_UTR_variant	Exon 1 of 9		NP_001316792.1
TRUB2	NM_001329862.2	c.-553G>T		upstream_gene_variant			NP_001316791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRUB2	ENST00000372890.6	c.60G>T	p.Gly20Gly	synonymous_variant	Exon 1 of 8	1	NM_015679.3	ENSP00000361982.4
TRUB2	ENST00000460320.1	n.65G>T		non_coding_transcript_exon_variant	Exon 1 of 9	2
COQ4	ENST00000608951.5	c.-510C>A		upstream_gene_variant		2		ENSP00000476323.1
COQ4	ENST00000609948.1	c.-510C>A		upstream_gene_variant		2		ENSP00000477292.1

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

GnomAD3 exomes AF: 0.0119 AC: 2990 AN: 251458 Hom.: 24 AF XY: 0.0131 AC XY: 1774 AN XY: 135914

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 SAS exome AF: 0.0204

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

Gnomad4 AFR exome AF: 0.00227

Gnomad4 AMR exome AF: 0.00825

Gnomad4 ASJ exome AF: 0.0113

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0208

Gnomad4 FIN exome AF: 0.00168

Gnomad4 NFE exome AF: 0.0173

Gnomad4 OTH exome AF: 0.0148

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

Gnomad4 AFR AF: 0.00245

Gnomad4 AMR AF: 0.00726

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0189

Gnomad4 FIN AF: 0.00141

Gnomad4 NFE AF: 0.0148

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00383 Hom.: 3

Bravo AF: 0.00978

EpiCase AF: 0.0159

EpiControl AF: 0.0146

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	9.4
DANN	Benign	0.97
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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

Publications

LitVar

Other links and lift over

dbSNP: rs11539570; hg19: chr9-131084628;