20-46686886-G-C

Variant names:

• chr20-46686886-G-C
• rs1164020767
• NM_033550.4:c.629C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_033550.4(TP53RK):​c.629C>G​(p.Thr210Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T210I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TP53RK NM_033550.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.67
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Galloway-Mowat syndrome 4

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• Galloway-Mowat syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033550.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP53RK	NM_033550.4	MANE Select	c.629C>G	p.Thr210Ser	missense	Exon 2 of 2	NP_291028.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP53RK	ENST00000372114.4	TSL:1 MANE Select	c.629C>G	p.Thr210Ser	missense	Exon 2 of 2	ENSP00000361186.3	Q96S44
	TP53RK	ENST00000372102.3	TSL:1	c.*268C>G		3_prime_UTR	Exon 2 of 2	ENSP00000361174.3	Q5JZ02

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461888 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112010

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.037	T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0069	T
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		7.7
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.20
Sift	Benign	0.049	D
Sift4G	Benign	0.073	T
Polyphen		0.96	D
Vest4		0.31
MutPred		0.56		Gain of disorder (P = 0.0608)
MVP		0.35
MPC		0.78
ClinPred		0.97	D
GERP RS		5.4
Varity_R		0.42
Mutation Taster		=53/47	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1164020767; hg19: chr20-45315525;