ENST00000939335.1:c.*189A>G – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000939335.1(TPRKB):c.*189A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 702,000 control chromosomes in the GnomAD database, including 141,587 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 27462 hom., cov: 29)

Exomes 𝑓: 0.64 ( 114125 hom. )

Consequence

TPRKB
ENST00000939335.1 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0380

Publications

4 publications found

Variant links:

Genes affected

TPRKB (HGNC:24259): (TP53RK binding protein) Enables protein kinase binding activity. Involved in tRNA threonylcarbamoyladenosine modification. Located in cytosol and nucleus. Part of EKC/KEOPS complex. Implicated in Galloway-Mowat syndrome 5. [provided by Alliance of Genome Resources, Apr 2022]

TPRKB Gene-Disease associations (from GenCC):

Galloway-Mowat syndrome 5
Inheritance: AR, Unknown Classification: STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
Galloway-Mowat syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TPRKB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 2-73729754-T-C is Benign according to our data. Variant chr2-73729754-T-C is described in ClinVar as Benign. ClinVar VariationId is 1289042.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000939335.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TPRKB	NM_016058.5	MANE Select	c.*189A>G	downstream_gene	N/A	NP_057142.1	Q9Y3C4-1
TPRKB	NM_001330386.2		c.*189A>G	downstream_gene	N/A	NP_001317315.1	Q9Y3C4-3
TPRKB	NM_001330387.2		c.*189A>G	downstream_gene	N/A	NP_001317316.1	Q9Y3C4-3

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
TPRKB	ENST00000939335.1	c.*189A>G	3_prime_UTR	Exon 6 of 6	ENSP00000609394.1
TPRKB	ENST00000939336.1	c.*189A>G	3_prime_UTR	Exon 5 of 5	ENSP00000609395.1
TPRKB	ENST00000965314.1	c.*189A>G	3_prime_UTR	Exon 5 of 5	ENSP00000635373.1

Frequencies

GnomAD3 genomes

AF:

0.594

AC:

89552

AN:

150860

Hom.:

27445

Cov.:

show subpopulations

Gnomad AFR

AF:

0.426

Gnomad AMI

AF:

0.718

Gnomad AMR

AF:

0.592

Gnomad ASJ

AF:

0.656

Gnomad EAS

AF:

0.695

Gnomad SAS

AF:

0.675

Gnomad FIN

AF:

0.705

Gnomad MID

AF:

0.680

Gnomad NFE

AF:

0.659

Gnomad OTH

AF:

0.618

GnomAD4 exome

AF:

0.639

AC:

351905

AN:

551032

Hom.:

114125

AF XY:

0.637

AC XY:

170306

AN XY:

267460

show subpopulations

African (AFR)

AF:

0.394

AC:

4383

AN:

11134

American (AMR)

AF:

0.499

AC:

2092

AN:

4194

Ashkenazi Jewish (ASJ)

AF:

0.638

AC:

4212

AN:

6606

East Asian (EAS)

AF:

0.618

AC:

5429

AN:

8780

South Asian (SAS)

AF:

0.635

AC:

15180

AN:

23902

European-Finnish (FIN)

AF:

0.663

AC:

5797

AN:

8738

Middle Eastern (MID)

AF:

0.640

AC:

911

AN:

1424

European-Non Finnish (NFE)

AF:

0.646

AC:

300477

AN:

465314

Other (OTH)

AF:

0.641

AC:

13424

AN:

20940

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

5897

11794

17692

23589

29486

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9132

18264

27396

36528

45660

<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:

0.594

AC:

89611

AN:

150968

Hom.:

27462

Cov.:

AF XY:

0.599

AC XY:

44117

AN XY:

73696

show subpopulations

African (AFR)

AF:

0.427

AC:

17594

AN:

41208

American (AMR)

AF:

0.591

AC:

8992

AN:

15214

Ashkenazi Jewish (ASJ)

AF:

0.656

AC:

2275

AN:

3468

East Asian (EAS)

AF:

0.695

AC:

3569

AN:

5132

South Asian (SAS)

AF:

0.675

AC:

3244

AN:

4806

European-Finnish (FIN)

AF:

0.705

AC:

7098

AN:

10074

Middle Eastern (MID)

AF:

0.684

AC:

201

AN:

294

European-Non Finnish (NFE)

AF:

0.659

AC:

44684

AN:

67756

Other (OTH)

AF:

0.618

AC:

1301

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

1751

3502

5254

7005

8756

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

754

1508

2262

3016

3770

<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:

0.622

Hom.:

3803

Bravo

AF:

0.577

Asia WGS

AF:

0.683

AC:

2376

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

4.1

(source)

DANN

Benign

0.41

PhyloP100

-0.038

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over