Genetic Variant NM_139169.5: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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139169.5. 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
	TRUB1	NM_139169.5	MANE Select	c.737-19G>C		intron	N/A	NP_631908.1	Q8WWH5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TRUB1	ENST00000298746.5	TSL:1 MANE Select	c.737-19G>C	intron	N/A	ENSP00000298746.3	Q8WWH5
TRUB1	ENST00000948779.1		c.875-19G>C	intron	N/A	ENSP00000618838.1
TRUB1	ENST00000900222.1		c.734-19G>C	intron	N/A	ENSP00000570281.1

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 v4.9

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over