rs144417465

Variant names:

• chr2-73730611-C-G
• NM_016058.5:c.390G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-73730611-C-G
• chr2-73730611-C-T

Variant summary

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

The NM_016058.5(TPRKB):​c.390G>C​(p.Gln130His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,439,664 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TPRKB NM_016058.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300

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.390G>C	p.Gln130His	missense_variant	Exon 4 of 5	ENST00000272424.11	NP_057142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPRKB	ENST00000272424.11	c.390G>C	p.Gln130His	missense_variant	Exon 4 of 5	1	NM_016058.5	ENSP00000272424.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1439664 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 715696

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000258

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	0.36
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;.;.
Eigen	Benign	0.12
Eigen_PC	Benign	-0.015
FATHMM_MKL	Benign	0.40	N
LIST_S2	Uncertain	0.88	D;.;D
M_CAP	Benign	0.0062	T
MetaRNN	Uncertain	0.49	T;T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.9	M;.;.
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.0	D;D;D
REVEL	Benign	0.28
Sift	Benign	0.034	D;D;D
Sift4G	Uncertain	0.049	D;T;T
Polyphen		1.0	D;D;D
Vest4		0.51
MutPred		0.51		Loss of catalytic residue at Q130 (P = 0.1193);.;.;
MVP		0.50
MPC		0.12
ClinPred		0.99	D
GERP RS		1.0
Varity_R		0.23
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr2-73957738;