2-73729997-A-T

Variant names:

• chr2-73729997-A-T
• rs7210
• NM_016058.5:c.474T>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016058.5(TPRKB):​c.474T>A​(p.Ile158Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I158I) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TPRKB NM_016058.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.754
• Publications: 21 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016058.5. 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.474T>A	p.Ile158Ile	synonymous	Exon 5 of 5	NP_057142.1	Q9Y3C4-1
	TPRKB	NM_001330386.2		c.591T>A	p.Ile197Ile	synonymous	Exon 6 of 6	NP_001317315.1	Q9Y3C4-3
	TPRKB	NM_001330387.2		c.591T>A	p.Ile197Ile	synonymous	Exon 6 of 6	NP_001317316.1	Q9Y3C4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPRKB	ENST00000272424.11	TSL:1 MANE Select	c.474T>A	p.Ile158Ile	synonymous	Exon 5 of 5	ENSP00000272424.5	Q9Y3C4-1
	TPRKB	ENST00000318190.7	TSL:5	c.591T>A	p.Ile197Ile	synonymous	Exon 6 of 6	ENSP00000325398.7	Q9Y3C4-3
	TPRKB	ENST00000409716.6	TSL:5	c.591T>A	p.Ile197Ile	synonymous	Exon 6 of 6	ENSP00000386936.2	Q9Y3C4-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1419844 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 704816

African (AFR) AF: 0.00 AC: 0 AN: 32406

American (AMR) AF: 0.00 AC: 0 AN: 38302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24678

East Asian (EAS) AF: 0.00 AC: 0 AN: 38610

South Asian (SAS) AF: 0.00 AC: 0 AN: 81274

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51710

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5642

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1088710

Other (OTH) AF: 0.00 AC: 0 AN: 58512

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 52149

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	1.7
DANN	Benign	0.74
PhyloP100		0.75
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.41		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.41		Position offset: 32

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

Other links and lift over

dbSNP: rs7210; hg19: chr2-73957124;