ENST00000939338.1:c.*129delA

Variant names:

• chr2-73729813-CT-C
• rs67805162
• ENST00000939338.1:c.*129delA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000939338.1(TPRKB):​c.*129delA variant causes a splice region change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.59 (24726 hom., cov: 0)
  • Exomes 𝑓: 0.46 (7531 hom.)
  • Failed GnomAD Quality Control
• Consequence: TPRKB ENST00000939338.1 splice_region
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00700
• Publications: 0 publications found

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]

TPRKB Gene-Disease associations (from GenCC):

• Galloway-Mowat syndrome 5

  Inheritance: AR, Unknown Classification: STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
• Galloway-Mowat syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 2-73729813-CT-C is Benign according to our data. Variant chr2-73729813-CT-C is described in ClinVar as Benign. ClinVar VariationId is 1242937.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000939338.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPRKB	NM_016058.5	MANE Select	c.*129delA		downstream_gene	N/A	NP_057142.1	Q9Y3C4-1
	TPRKB	NM_001330386.2		c.*129delA		downstream_gene	N/A	NP_001317315.1	Q9Y3C4-3
	TPRKB	NM_001330387.2		c.*129delA		downstream_gene	N/A	NP_001317316.1	Q9Y3C4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPRKB	ENST00000939338.1		c.*129delA		splice_region	Exon 7 of 7	ENSP00000609397.1
	TPRKB	ENST00000939338.1		c.*129delA		3_prime_UTR	Exon 7 of 7	ENSP00000609397.1
	TPRKB	ENST00000939335.1		c.*129delA		3_prime_UTR	Exon 6 of 6	ENSP00000609394.1

Frequencies

GnomAD3 genomes AF: 0.592 AC: 83157 AN: 140508 Hom.: 24742 Cov.: 0

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.758

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.649

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.664

Gnomad NFE AF: 0.654

Gnomad OTH AF: 0.610

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.463 AC: 362461 AN: 782184 Hom.: 7531 Cov.: 0 AF XY: 0.462 AC XY: 171534 AN XY: 371162

African (AFR) AF: 0.393 AC: 6154 AN: 15648

American (AMR) AF: 0.397 AC: 1548 AN: 3898

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 3573 AN: 7952

East Asian (EAS) AF: 0.445 AC: 5539 AN: 12450

South Asian (SAS) AF: 0.447 AC: 11199 AN: 25032

European-Finnish (FIN) AF: 0.406 AC: 4327 AN: 10648

Middle Eastern (MID) AF: 0.452 AC: 835 AN: 1846

European-Non Finnish (NFE) AF: 0.468 AC: 316120 AN: 676018

Other (OTH) AF: 0.459 AC: 13166 AN: 28692

GnomAD4 genome AF: 0.592 AC: 83139 AN: 140502 Hom.: 24726 Cov.: 0 AF XY: 0.596 AC XY: 40267 AN XY: 67618

African (AFR) AF: 0.432 AC: 16361 AN: 37830

American (AMR) AF: 0.592 AC: 8388 AN: 14174

Ashkenazi Jewish (ASJ) AF: 0.649 AC: 2196 AN: 3386

East Asian (EAS) AF: 0.696 AC: 3422 AN: 4920

South Asian (SAS) AF: 0.674 AC: 2976 AN: 4416

European-Finnish (FIN) AF: 0.683 AC: 5167 AN: 7566

Middle Eastern (MID) AF: 0.661 AC: 181 AN: 274

European-Non Finnish (NFE) AF: 0.654 AC: 42582 AN: 65090

Other (OTH) AF: 0.609 AC: 1187 AN: 1950

Alfa AF: 0.431 Hom.: 949

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.0070
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs67805162; hg19: chr2-73956940; COSMIC: COSV55541019;