NM_016058.5:c.481T>C

Variant names:

• chr2-73729990-A-G
• rs763140886
• NM_016058.5:c.481T>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_016058.5(TPRKB):​c.481T>C​(p.Leu161Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000697 in 1,578,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000063 (0 hom.)
• Consequence: TPRKB NM_016058.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.34
• 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 2-73729990-A-G is Benign according to our data. Variant chr2-73729990-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3610245.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.34 with no splicing effect.

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.481T>C	p.Leu161Leu	synonymous	Exon 5 of 5	NP_057142.1	Q9Y3C4-1
	TPRKB	NM_001330386.2		c.598T>C	p.Leu200Leu	synonymous	Exon 6 of 6	NP_001317315.1	Q9Y3C4-3
	TPRKB	NM_001330387.2		c.598T>C	p.Leu200Leu	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.481T>C	p.Leu161Leu	synonymous	Exon 5 of 5	ENSP00000272424.5	Q9Y3C4-1
	TPRKB	ENST00000318190.7	TSL:5	c.598T>C	p.Leu200Leu	synonymous	Exon 6 of 6	ENSP00000325398.7	Q9Y3C4-3
	TPRKB	ENST00000409716.6	TSL:5	c.598T>C	p.Leu200Leu	synonymous	Exon 6 of 6	ENSP00000386936.2	Q9Y3C4-3

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152196 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000133 AC: 3 AN: 226042 AF XY: 0.00000816

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000193

Gnomad OTH exome AF: 0.000181

GnomAD4 exome AF: 0.00000631 AC: 9 AN: 1425700 Hom.: 0 Cov.: 30 AF XY: 0.00000706 AC XY: 5 AN XY: 707976

African (AFR) AF: 0.00 AC: 0 AN: 32602

American (AMR) AF: 0.00 AC: 0 AN: 39082

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24780

East Asian (EAS) AF: 0.00 AC: 0 AN: 38846

South Asian (SAS) AF: 0.00 AC: 0 AN: 82036

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51954

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5656

European-Non Finnish (NFE) AF: 0.00000733 AC: 8 AN: 1091944

Other (OTH) AF: 0.0000170 AC: 1 AN: 58800

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152314 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74472

African (AFR) AF: 0.00 AC: 0 AN: 41568

American (AMR) AF: 0.00 AC: 0 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000756

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.4
DANN	Benign	0.74
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs763140886; hg19: chr2-73957117;