20-46686707-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.645

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
TP53RK	NM_033550.4	c.*46G>A		3_prime_UTR_variant	2/2	ENST00000372114.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TP53RK	ENST00000372114.4	c.*46G>A		3_prime_UTR_variant	2/2	1	NM_033550.4	P1
TP53RK	ENST00000372102.3	c.*447G>A		3_prime_UTR_variant	2/2	1

Frequencies

GnomAD3 genomes AF: 0.0919 AC: 13980 AN: 152074 Hom.: 1241 Cov.: 33

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

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.: 20 AF XY: 0.0393 AC XY: 25880 AN XY: 658038

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.: 33 AF XY: 0.0917 AC XY: 6825 AN XY: 74428

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

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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

Other links and lift over

dbSNP: rs45544334; hg19: chr20-45315346;