Genetic Variant TRUB1:c.737-19G>C (chr10-114974310-G-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_139169.5(TRUB1):c.737-19G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0605 in 1,605,248 control chromosomes in the GnomAD database, including 9,813 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 0.16 ( 4656 hom., cov: 32)

Exomes 𝑓: 0.050 ( 5157 hom. )

Consequence

TRUB1
NM_139169.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.20

Publications

3 publications found

Variant links:

Genes affected

TRUB1 (HGNC:16060): (TruB pseudouridine synthase family member 1) 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]

TRUB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.24).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRUB1	NM_139169.5 link	c.737-19G>C		intron_variant	Intron 6 of 7	ENST00000298746.5	NP_631908.1	Q8WWH5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRUB1	ENST00000298746.5 link	c.737-19G>C		intron_variant	Intron 6 of 7	1	NM_139169.5	ENSP00000298746.3		Q8WWH5

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24223

AN:

152066

Hom.:

4646

Cov.:

show subpopulations

Gnomad AFR

AF:

0.461

Gnomad AMI

AF:

0.0537

Gnomad AMR

AF:

0.0920

Gnomad ASJ

AF:

0.109

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0139

Gnomad FIN

AF:

0.0144

Gnomad MID

AF:

0.0732

Gnomad NFE

AF:

0.0411

Gnomad OTH

AF:

0.143

GnomAD2 exomes

AF:

0.0657

AC:

16388

AN:

249518

AF XY:

0.0573

show subpopulations

Gnomad AFR exome

AF:

0.467

Gnomad AMR exome

AF:

0.0481

Gnomad ASJ exome

AF:

0.116

Gnomad EAS exome

AF:

0.00104

Gnomad FIN exome

AF:

0.0156

Gnomad NFE exome

AF:

0.0436

Gnomad OTH exome

AF:

0.0570

GnomAD4 exome

AF:

0.0501

AC:

72780

AN:

1453064

Hom.:

5157

Cov.:

AF XY:

0.0478

AC XY:

34597

AN XY:

723342

show subpopulations

African (AFR)

AF:

0.464

AC:

15351

AN:

33052

American (AMR)

AF:

0.0535

AC:

2378

AN:

44486

Ashkenazi Jewish (ASJ)

AF:

0.110

AC:

2852

AN:

25982

East Asian (EAS)

AF:

0.000506

AC:

AN:

39546

South Asian (SAS)

AF:

0.0147

AC:

1264

AN:

85798

European-Finnish (FIN)

AF:

0.0145

AC:

775

AN:

53340

Middle Eastern (MID)

AF:

0.0807

AC:

461

AN:

5716

European-Non Finnish (NFE)

AF:

0.0412

AC:

45570

AN:

1105122

Other (OTH)

AF:

0.0685

AC:

4109

AN:

60022

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

2584

5169

7753

10338

12922

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1886

3772

5658

7544

9430

<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:

0.160

AC:

24274

AN:

152184

Hom.:

4656

Cov.:

AF XY:

0.155

AC XY:

11500

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.461

AC:

19110

AN:

41484

American (AMR)

AF:

0.0917

AC:

1400

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.109

AC:

379

AN:

3470

East Asian (EAS)

AF:

0.00116

AC:

AN:

5186

South Asian (SAS)

AF:

0.0131

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0144

AC:

153

AN:

10614

Middle Eastern (MID)

AF:

0.0685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0411

AC:

2795

AN:

68014

Other (OTH)

AF:

0.141

AC:

299

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

782

1564

2345

3127

3909

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

212

424

636

848

1060

<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:

0.0491

Hom.:

135

Bravo

AF:

0.180

Asia WGS

AF:

0.0350

AC:

123

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.76

PhyloP100

3.2

Mutation Taster

=100/0

polymorphism (auto)

(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

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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