NM_016058.5:c.452T>C

Variant names:

• chr2-73730019-A-G
• NM_016058.5:c.452T>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016058.5(TPRKB):​c.452T>C​(p.Leu151Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000707 in 1,415,056 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: TPRKB NM_016058.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.03

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPRKB	NM_016058.5	c.452T>C	p.Leu151Pro	missense_variant	Exon 5 of 5	ENST00000272424.11	NP_057142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPRKB	ENST00000272424.11	c.452T>C	p.Leu151Pro	missense_variant	Exon 5 of 5	1	NM_016058.5	ENSP00000272424.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.07e-7 AC: 1 AN: 1415056 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 702384

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.20e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000612 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 26, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.452T>C (p.L151P) alteration is located in exon 5 (coding exon 4) of the TPRKB gene. This alteration results from a T to C substitution at nucleotide position 452, causing the leucine (L) at amino acid position 151 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.39	T;.;.
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	T;.;T
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.68	D;D;D
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	1.9	L;.;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-4.5	D;D;D
REVEL	Uncertain	0.42
Sift	Uncertain	0.012	D;D;D
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		0.99	D;D;D
Vest4		0.62
MVP		0.79
MPC		0.13
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.86
gMVP		0.79

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-73957146;