2-73729813-CTTTTTT-CTTTTTTTTTT

Variant names:

• chr2-73729813-C-CTTTT
• rs67805162
• ENST00000939338.1:c.*126_*129dupAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000939338.1(TPRKB):​c.*126_*129dupAAAA variant causes a splice region change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000025 (0 hom.)
• Consequence: TPRKB ENST00000939338.1 splice_region
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.*129_*130insAAAA		downstream_gene	N/A	NP_057142.1	Q9Y3C4-1
	TPRKB	NM_001330386.2		c.*129_*130insAAAA		downstream_gene	N/A	NP_001317315.1	Q9Y3C4-3
	TPRKB	NM_001330387.2		c.*129_*130insAAAA		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.*126_*129dupAAAA		splice_region	Exon 7 of 7	ENSP00000609397.1
	TPRKB	ENST00000939338.1		c.*126_*129dupAAAA		3_prime_UTR	Exon 7 of 7	ENSP00000609397.1
	TPRKB	ENST00000939335.1		c.*126_*129dupAAAA		3_prime_UTR	Exon 6 of 6	ENSP00000609394.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000252 AC: 2 AN: 794470 Hom.: 0 Cov.: 0 AF XY: 0.00000265 AC XY: 1 AN XY: 377072

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 16130

American (AMR) AF: 0.00 AC: 0 AN: 3924

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8008

East Asian (EAS) AF: 0.00 AC: 0 AN: 12528

South Asian (SAS) AF: 0.00 AC: 0 AN: 25274

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10688

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1874

European-Non Finnish (NFE) AF: 0.00000291 AC: 2 AN: 686976

Other (OTH) AF: 0.00 AC: 0 AN: 29068

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.0070

Splicing

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

Other links and lift over

dbSNP: rs67805162; hg19: chr2-73956940;