rs140073724

Variant names:

• chr2-73730588-T-C
• rs140073724
• NM_016058.5:c.413A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-73730588-T-C
• chr2-73730588-T-G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_016058.5(TPRKB):​c.413A>G​(p.Glu138Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000219 in 1,590,920 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00022 (3 hom.)
• Consequence: TPRKB NM_016058.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.20
• Publications: 5 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008947223).
• BP6: Variant 2-73730588-T-C is Benign according to our data. Variant chr2-73730588-T-C is described in ClinVar as Benign. ClinVar VariationId is 3634931.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 3 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.413A>G	p.Glu138Gly	missense	Exon 4 of 5	NP_057142.1	Q9Y3C4-1
	TPRKB	NM_001330386.2		c.530A>G	p.Glu177Gly	missense	Exon 5 of 6	NP_001317315.1	Q9Y3C4-3
	TPRKB	NM_001330387.2		c.530A>G	p.Glu177Gly	missense	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.413A>G	p.Glu138Gly	missense	Exon 4 of 5	ENSP00000272424.5	Q9Y3C4-1
	TPRKB	ENST00000318190.7	TSL:5	c.530A>G	p.Glu177Gly	missense	Exon 5 of 6	ENSP00000325398.7	Q9Y3C4-3
	TPRKB	ENST00000409716.6	TSL:5	c.530A>G	p.Glu177Gly	missense	Exon 5 of 6	ENSP00000386936.2	Q9Y3C4-3

Frequencies

GnomAD3 genomes AF: 0.000230 AC: 35 AN: 152238 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00806

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000426 AC: 97 AN: 227776 AF XY: 0.000421

Gnomad AFR exome AF: 0.0000660

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00879

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000839

Gnomad OTH exome AF: 0.000720

GnomAD4 exome AF: 0.000218 AC: 314 AN: 1438682 Hom.: 3 Cov.: 29 AF XY: 0.000222 AC XY: 159 AN XY: 715358

African (AFR) AF: 0.00 AC: 0 AN: 31858

American (AMR) AF: 0.00 AC: 0 AN: 38694

Ashkenazi Jewish (ASJ) AF: 0.00858 AC: 220 AN: 25654

East Asian (EAS) AF: 0.00 AC: 0 AN: 38928

South Asian (SAS) AF: 0.00 AC: 0 AN: 80726

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52874

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5024

European-Non Finnish (NFE) AF: 0.0000425 AC: 47 AN: 1105404

Other (OTH) AF: 0.000790 AC: 47 AN: 59520

GnomAD4 genome AF: 0.000230 AC: 35 AN: 152238 Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14 AN XY: 74372

African (AFR) AF: 0.0000241 AC: 1 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00806 AC: 28 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68044

Other (OTH) AF: 0.000957 AC: 2 AN: 2090

Alfa AF: 0.000450 Hom.: 0

Bravo AF: 0.000215

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000338 AC: 41

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
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Benign	0.045
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.0089	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.2
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.10
Sift	Benign	0.088	T
Sift4G	Benign	0.085	T
Polyphen		0.27	B
Vest4		0.36
MVP		0.50
MPC		0.040
ClinPred		0.069	T
GERP RS		5.2
Varity_R		0.37
gMVP		0.29
Mutation Taster		=81/19	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: rs140073724; hg19: chr2-73957715;