2-73730100-T-A

Position:

• chr2-73730100-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016058.5(TPRKB):​c.442-71A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 1,421,978 control chromosomes in the GnomAD database, including 287,025 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (24430 hom., cov: 32)
  • Exomes 𝑓: 0.64 (262595 hom.)
• Consequence: TPRKB NM_016058.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.792

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 2-73730100-T-A is Benign according to our data. Variant chr2-73730100-T-A is described in ClinVar as [Benign]. Clinvar id is 1290163.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPRKB	NM_016058.5	c.442-71A>T		intron_variant		ENST00000272424.11	NP_057142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPRKB	ENST00000272424.11	c.442-71A>T		intron_variant		1	NM_016058.5	ENSP00000272424	P1

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80426 AN: 151866 Hom.: 24434 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.568

GnomAD4 exome AF: 0.638 AC: 810051 AN: 1269994 Hom.: 262595 Cov.: 20 AF XY: 0.639 AC XY: 399528 AN XY: 625346

Gnomad4 AFR exome AF: 0.174

Gnomad4 AMR exome AF: 0.530

Gnomad4 ASJ exome AF: 0.647

Gnomad4 EAS exome AF: 0.670

Gnomad4 SAS exome AF: 0.664

Gnomad4 FIN exome AF: 0.688

Gnomad4 NFE exome AF: 0.648

Gnomad4 OTH exome AF: 0.630

GnomAD4 genome AF: 0.529 AC: 80425 AN: 151984 Hom.: 24430 Cov.: 32 AF XY: 0.537 AC XY: 39894 AN XY: 74292

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.566

Gnomad4 ASJ AF: 0.642

Gnomad4 EAS AF: 0.697

Gnomad4 SAS AF: 0.675

Gnomad4 FIN AF: 0.705

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.569

Alfa AF: 0.550 Hom.: 2472

Bravo AF: 0.503

Asia WGS AF: 0.663 AC: 2297 AN: 3464

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	11
DANN	Benign	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

LitVar

Other links and lift over

dbSNP: rs13003035; hg19: chr2-73957227;