20-46686760-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_033550.4(TP53RK):c.755T>C(p.Val252Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Consequence
TP53RK
NM_033550.4 missense
NM_033550.4 missense
Scores
1
8
10
Clinical Significance
Conservation
PhyloP100: 9.00
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.28108913).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TP53RK | NM_033550.4 | c.755T>C | p.Val252Ala | missense_variant | 2/2 | ENST00000372114.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TP53RK | ENST00000372114.4 | c.755T>C | p.Val252Ala | missense_variant | 2/2 | 1 | NM_033550.4 | P1 | |
TP53RK | ENST00000372102.3 | c.*394T>C | 3_prime_UTR_variant | 2/2 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 05, 2022 | This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 252 of the TP53RK protein (p.Val252Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TP53RK-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Benign
D
Sift4G
Benign
T
Polyphen
P
Vest4
MutPred
Loss of stability (P = 0.0701);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at