rs11539570

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BS1BS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.334

Publications

8 publications found

Variant links:

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]

TRUB2 links:

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

COQ4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes

AF:

0.00915

AC:

1393

AN:

152162

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0159

AC XY:

11568

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.00227

AC:

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:

AN:

39700

South Asian (SAS)

AF:

0.0208

AC:

1792

AN:

86256

European-Finnish (FIN)

AF:

0.00168

AC:

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

1164

2328

3492

4656

5820

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

756

1512

2268

3024

3780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00913

AC:

1390

AN:

152280

Hom.:

Cov.:

AF XY:

0.00842

AC XY:

627

AN XY:

74448

show subpopulations

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:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.0189

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00141

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0148

AC:

1007

AN:

68024

Other (OTH)

AF:

0.0104

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

136

205

273

341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00343

Hom.:

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

(source)

DANN

Benign

0.97

PhyloP100

-0.33

PromoterAI

0.0064

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over