Variant 2-73729997-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_016058.5(TPRKB):c.474T>C(p.Ile158=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 1,566,616 control chromosomes in the GnomAD database, including 324,466 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 26579 hom., cov: 32)

Exomes 𝑓: 0.65 ( 297887 hom. )

Consequence

TPRKB
NM_016058.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.754

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 2-73729997-A-G is Benign according to our data. Variant chr2-73729997-A-G is described in ClinVar as [Benign]. Clinvar id is 1253010.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.754 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPRKB	NM_016058.5 linkuse as main transcript	c.474T>C	p.Ile158=	synonymous_variant	5/5	ENST00000272424.11	NP_057142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPRKB	ENST00000272424.11 linkuse as main transcript	c.474T>C	p.Ile158=	synonymous_variant	5/5	1	NM_016058.5	ENSP00000272424	P1	Q9Y3C4-1

Frequencies

GnomAD3 genomes

AF:

0.576

AC:

87527

AN:

151940

Hom.:

26572

Cov.:

show subpopulations

Gnomad AFR

AF:

0.365

Gnomad AMI

AF:

0.724

Gnomad AMR

AF:

0.586

Gnomad ASJ

AF:

0.641

Gnomad EAS

AF:

0.697

Gnomad SAS

AF:

0.676

Gnomad FIN

AF:

0.706

Gnomad MID

AF:

0.674

Gnomad NFE

AF:

0.659

Gnomad OTH

AF:

0.604

GnomAD3 exomes

AF:

0.628

AC:

140375

AN:

223410

Hom.:

44934

AF XY:

0.637

AC XY:

77250

AN XY:

121228

show subpopulations

Gnomad AFR exome

AF:

0.349

Gnomad AMR exome

AF:

0.541

Gnomad ASJ exome

AF:

0.647

Gnomad EAS exome

AF:

0.703

Gnomad SAS exome

AF:

0.669

Gnomad FIN exome

AF:

0.695

Gnomad NFE exome

AF:

0.653

Gnomad OTH exome

AF:

0.642

GnomAD4 exome

AF:

0.646

AC:

913885

AN:

1414558

Hom.:

297887

Cov.:

AF XY:

0.647

AC XY:

454507

AN XY:

702184

show subpopulations

Gnomad4 AFR exome

AF:

0.349

Gnomad4 AMR exome

AF:

0.543

Gnomad4 ASJ exome

AF:

0.651

Gnomad4 EAS exome

AF:

0.681

Gnomad4 SAS exome

AF:

0.668

Gnomad4 FIN exome

AF:

0.697

Gnomad4 NFE exome

AF:

0.653

Gnomad4 OTH exome

AF:

0.647

GnomAD4 genome

AF:

0.576

AC:

87572

AN:

152058

Hom.:

26579

Cov.:

AF XY:

0.582

AC XY:

43266

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.365

Gnomad4 AMR

AF:

0.585

Gnomad4 ASJ

AF:

0.641

Gnomad4 EAS

AF:

0.697

Gnomad4 SAS

AF:

0.676

Gnomad4 FIN

AF:

0.706

Gnomad4 NFE

AF:

0.659

Gnomad4 OTH

AF:

0.604

Alfa

AF:

0.639

Hom.:

46469

Bravo

AF:

0.556

Asia WGS

AF:

0.675

AC:

2348

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Galloway-Mowat syndrome 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

8.6

DANN

Benign

0.77

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over