NM_016058.5:c.390G>A

Variant names:

• chr2-73730611-C-T
• rs144417465
• NM_016058.5:c.390G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_016058.5(TPRKB):​c.390G>A​(p.Gln130Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000525 in 1,591,900 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00034 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00054 (13 hom.)
• Consequence: TPRKB NM_016058.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0300
• Publications: 3 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 2-73730611-C-T is Benign according to our data. Variant chr2-73730611-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 764552.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.03 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.000544 (783/1439658) while in subpopulation EAS AF = 0.0191 (739/38776). AF 95% confidence interval is 0.0179. There are 13 homozygotes in GnomAdExome4. There are 372 alleles in the male GnomAdExome4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 13 Unknown,AR gene

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.390G>A	p.Gln130Gln	synonymous	Exon 4 of 5	NP_057142.1	Q9Y3C4-1
	TPRKB	NM_001330386.2		c.507G>A	p.Gln169Gln	synonymous	Exon 5 of 6	NP_001317315.1	Q9Y3C4-3
	TPRKB	NM_001330387.2		c.507G>A	p.Gln169Gln	synonymous	Exon 5 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.390G>A	p.Gln130Gln	synonymous	Exon 4 of 5	ENSP00000272424.5	Q9Y3C4-1
	TPRKB	ENST00000318190.7	TSL:5	c.507G>A	p.Gln169Gln	synonymous	Exon 5 of 6	ENSP00000325398.7	Q9Y3C4-3
	TPRKB	ENST00000409716.6	TSL:5	c.507G>A	p.Gln169Gln	synonymous	Exon 5 of 6	ENSP00000386936.2	Q9Y3C4-3

Frequencies

GnomAD3 genomes AF: 0.000342 AC: 52 AN: 152124 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: 0.00980

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000483 AC: 111 AN: 229904 AF XY: 0.000450

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000693

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00617

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000186

Gnomad OTH exome AF: 0.000356

GnomAD4 exome AF: 0.000544 AC: 783 AN: 1439658 Hom.: 13 Cov.: 29 AF XY: 0.000520 AC XY: 372 AN XY: 715692

African (AFR) AF: 0.00 AC: 0 AN: 31884

American (AMR) AF: 0.0000764 AC: 3 AN: 39280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25680

East Asian (EAS) AF: 0.0191 AC: 739 AN: 38776

South Asian (SAS) AF: 0.0000124 AC: 1 AN: 80902

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5432

European-Non Finnish (NFE) AF: 0.00000271 AC: 3 AN: 1105146

Other (OTH) AF: 0.000621 AC: 37 AN: 59594

GnomAD4 genome AF: 0.000342 AC: 52 AN: 152242 Hom.: 0 Cov.: 32 AF XY: 0.000417 AC XY: 31 AN XY: 74426

African (AFR) AF: 0.00 AC: 0 AN: 41544

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00982 AC: 51 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000134 Hom.: 0

Bravo AF: 0.000385

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Galloway-Mowat syndrome 5 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	4.8
DANN	Benign	0.72
PhyloP100		-0.030
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs144417465; hg19: chr2-73957738; COSMIC: COSV55541970; COSMIC: COSV55541970;