2-73729968-C-T

Variant names:

• chr2-73729968-C-T
• NM_016058.5:c.503G>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_016058.5(TPRKB):​c.503G>A​(p.Arg168Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000704 in 1,420,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: TPRKB NM_016058.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.97

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.88

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPRKB	NM_016058.5	c.503G>A	p.Arg168Lys	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.503G>A	p.Arg168Lys	missense_variant	Exon 5 of 5	1	NM_016058.5	ENSP00000272424.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.04e-7 AC: 1 AN: 1420110 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 704572

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000255

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;.;.
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D;.;D
M_CAP	Benign	0.016	T
MetaRNN	Pathogenic	0.88	D;D;D
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.4	M;.;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-2.3	N;N;N
REVEL	Benign	0.20
Sift	Benign	0.092	T;T;T
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.97	D;D;D
Vest4		0.74
MutPred		0.80		Gain of methylation at R168 (P = 0.0101);.;.;
MVP		0.62
MPC		0.15
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.77
gMVP		0.64

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: chr2-73957095;