ENST00000939338.1:c.*129delA – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The ENST00000939338.1(TPRKB):c.*129delA variant causes a splice region change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.59 ( 24726 hom., cov: 0)

Exomes 𝑓: 0.46 ( 7531 hom. )

Failed GnomAD Quality Control

Consequence

TPRKB
ENST00000939338.1 splice_region

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.00700

Publications

0 publications found

Variant links:

COSMIC-nc: COSV55541019

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 -10 ACMG points.

BP6

Variant 2-73729813-CT-C is Benign according to our data. Variant chr2-73729813-CT-C is described in ClinVar as Benign. ClinVar VariationId is 1242937.Status of the report is criteria_provided_single_submitter, 1 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: ENST00000939338.1. 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.*129delA	downstream_gene	N/A	NP_057142.1	Q9Y3C4-1
TPRKB	NM_001330386.2		c.*129delA	downstream_gene	N/A	NP_001317315.1	Q9Y3C4-3
TPRKB	NM_001330387.2		c.*129delA	downstream_gene	N/A	NP_001317316.1	Q9Y3C4-3

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
TPRKB	ENST00000939338.1	c.*129delA	splice_region	Exon 7 of 7	ENSP00000609397.1
TPRKB	ENST00000939338.1	c.*129delA	3_prime_UTR	Exon 7 of 7	ENSP00000609397.1
TPRKB	ENST00000939335.1	c.*129delA	3_prime_UTR	Exon 6 of 6	ENSP00000609394.1

Frequencies

GnomAD3 genomes

AF:

0.592

AC:

83157

AN:

140508

Hom.:

24742

Cov.:

show subpopulations

Gnomad AFR

AF:

0.432

Gnomad AMI

AF:

0.758

Gnomad AMR

AF:

0.592

Gnomad ASJ

AF:

0.649

Gnomad EAS

AF:

0.696

Gnomad SAS

AF:

0.674

Gnomad FIN

AF:

0.683

Gnomad MID

AF:

0.664

Gnomad NFE

AF:

0.654

Gnomad OTH

AF:

0.610

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.463

AC:

362461

AN:

782184

Hom.:

7531

Cov.:

AF XY:

0.462

AC XY:

171534

AN XY:

371162

show subpopulations

African (AFR)

AF:

0.393

AC:

6154

AN:

15648

American (AMR)

AF:

0.397

AC:

1548

AN:

3898

Ashkenazi Jewish (ASJ)

AF:

0.449

AC:

3573

AN:

7952

East Asian (EAS)

AF:

0.445

AC:

5539

AN:

12450

South Asian (SAS)

AF:

0.447

AC:

11199

AN:

25032

European-Finnish (FIN)

AF:

0.406

AC:

4327

AN:

10648

Middle Eastern (MID)

AF:

0.452

AC:

835

AN:

1846

European-Non Finnish (NFE)

AF:

0.468

AC:

316120

AN:

676018

Other (OTH)

AF:

0.459

AC:

13166

AN:

28692

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

10974

21949

32923

43898

54872

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14888

29776

44664

59552

74440

<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:

0.592

AC:

83139

AN:

140502

Hom.:

24726

Cov.:

AF XY:

0.596

AC XY:

40267

AN XY:

67618

show subpopulations

African (AFR)

AF:

0.432

AC:

16361

AN:

37830

American (AMR)

AF:

0.592

AC:

8388

AN:

14174

Ashkenazi Jewish (ASJ)

AF:

0.649

AC:

2196

AN:

3386

East Asian (EAS)

AF:

0.696

AC:

3422

AN:

4920

South Asian (SAS)

AF:

0.674

AC:

2976

AN:

4416

European-Finnish (FIN)

AF:

0.683

AC:

5167

AN:

7566

Middle Eastern (MID)

AF:

0.661

AC:

181

AN:

274

European-Non Finnish (NFE)

AF:

0.654

AC:

42582

AN:

65090

Other (OTH)

AF:

0.609

AC:

1187

AN:

1950

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1546

3092

4637

6183

7729

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

704

1408

2112

2816

3520

<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:

0.431

Hom.:

949

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.0070

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