2-73729754-T-C

Position:

• chr2-73729754-T-C

Variant summary

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

The ENST00000463231.5(TPRKB):​n.439-449A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 702,000 control chromosomes in the GnomAD database, including 141,587 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (27462 hom., cov: 29)
  • Exomes 𝑓: 0.64 (114125 hom.)
• Consequence: TPRKB ENST00000463231.5 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0380

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=-0.97).
• BP6: Variant 2-73729754-T-C is Benign according to our data. Variant chr2-73729754-T-C is described in ClinVar as [Benign]. Clinvar id is 1289042.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPRKB	ENST00000463231.5	n.439-449A>G		intron_variant, non_coding_transcript_variant		2
TPRKB	ENST00000484969.5	n.521-449A>G		intron_variant, non_coding_transcript_variant		4
TPRKB	ENST00000489476.5	n.335-449A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.594 AC: 89552 AN: 150860 Hom.: 27445 Cov.: 29

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.618

GnomAD4 exome AF: 0.639 AC: 351905 AN: 551032 Hom.: 114125 AF XY: 0.637 AC XY: 170306 AN XY: 267460

Gnomad4 AFR exome AF: 0.394

Gnomad4 AMR exome AF: 0.499

Gnomad4 ASJ exome AF: 0.638

Gnomad4 EAS exome AF: 0.618

Gnomad4 SAS exome AF: 0.635

Gnomad4 FIN exome AF: 0.663

Gnomad4 NFE exome AF: 0.646

Gnomad4 OTH exome AF: 0.641

GnomAD4 genome AF: 0.594 AC: 89611 AN: 150968 Hom.: 27462 Cov.: 29 AF XY: 0.599 AC XY: 44117 AN XY: 73696

Gnomad4 AFR AF: 0.427

Gnomad4 AMR AF: 0.591

Gnomad4 ASJ AF: 0.656

Gnomad4 EAS AF: 0.695

Gnomad4 SAS AF: 0.675

Gnomad4 FIN AF: 0.705

Gnomad4 NFE AF: 0.659

Gnomad4 OTH AF: 0.618

Alfa AF: 0.622 Hom.: 3803

Bravo AF: 0.577

Asia WGS AF: 0.683 AC: 2376 AN: 3478

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	-0.97
CADD	Benign	4.1
DANN	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12997568; hg19: chr2-73956881;