Variant 20-46686707-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_033550.4(TP53RK):c.*46G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0447 in 1,471,316 control chromosomes in the GnomAD database, including 3,191 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.092 ( 1241 hom., cov: 33)

Exomes 𝑓: 0.039 ( 1950 hom. )

Consequence

TP53RK
NM_033550.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.645

Variant links:

Genes affected

TP53RK (HGNC:16197): (TP53 regulating kinase) Enables p53 binding activity and protein serine/threonine kinase activity. Involved in protein phosphorylation. Located in cytoplasm and nucleus. Part of EKC/KEOPS complex. Implicated in Galloway-Mowat syndrome 4. [provided by Alliance of Genome Resources, Apr 2022]

TP53RK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 20-46686707-C-T is Benign according to our data. Variant chr20-46686707-C-T is described in ClinVar as [Benign]. Clinvar id is 1229334.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TP53RK	NM_033550.4 link	c.*46G>A		3_prime_UTR_variant	2/2	ENST00000372114.4	NP_291028.3	Q96S44

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TP53RK	ENST00000372114 link	c.*46G>A		3_prime_UTR_variant	2/2	1	NM_033550.4	ENSP00000361186.3		Q96S44
TP53RK	ENST00000372102 link	c.*447G>A		3_prime_UTR_variant	2/2	1		ENSP00000361174.3		Q5JZ02

Frequencies

GnomAD3 genomes

AF:

0.0919

AC:

13980

AN:

152074

Hom.:

1241

Cov.:

show subpopulations

Gnomad AFR

AF:

0.228

Gnomad AMI

AF:

0.113

Gnomad AMR

AF:

0.0785

Gnomad ASJ

AF:

0.0496

Gnomad EAS

AF:

0.0783

Gnomad SAS

AF:

0.0708

Gnomad FIN

AF:

0.0312

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0272

Gnomad OTH

AF:

0.0722

GnomAD3 exomes

AF:

0.0638

AC:

14300

AN:

224120

Hom.:

866

AF XY:

0.0576

AC XY:

6953

AN XY:

120780

show subpopulations

Gnomad AFR exome

AF:

0.229

Gnomad AMR exome

AF:

0.117

Gnomad ASJ exome

AF:

0.0427

Gnomad EAS exome

AF:

0.0861

Gnomad SAS exome

AF:

0.0707

Gnomad FIN exome

AF:

0.0317

Gnomad NFE exome

AF:

0.0280

Gnomad OTH exome

AF:

0.0426

GnomAD4 exome

AF:

0.0392

AC:

51747

AN:

1319124

Hom.:

1950

Cov.:

AF XY:

0.0393

AC XY:

25880

AN XY:

658038

show subpopulations

Gnomad4 AFR exome

AF:

0.231

Gnomad4 AMR exome

AF:

0.110

Gnomad4 ASJ exome

AF:

0.0442

Gnomad4 EAS exome

AF:

0.0762

Gnomad4 SAS exome

AF:

0.0641

Gnomad4 FIN exome

AF:

0.0333

Gnomad4 NFE exome

AF:

0.0274

Gnomad4 OTH exome

AF:

0.0458

GnomAD4 genome

AF:

0.0919

AC:

13993

AN:

152192

Hom.:

1241

Cov.:

AF XY:

0.0917

AC XY:

6825

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.227

Gnomad4 AMR

AF:

0.0783

Gnomad4 ASJ

AF:

0.0496

Gnomad4 EAS

AF:

0.0787

Gnomad4 SAS

AF:

0.0715

Gnomad4 FIN

AF:

0.0312

Gnomad4 NFE

AF:

0.0272

Gnomad4 OTH

AF:

0.0720

Alfa

AF:

0.0513

Hom.:

110

Bravo

AF:

0.103

Asia WGS

AF:

0.105

AC:

364

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.5

DANN

Benign

0.66

Splicing

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