Genetic Variant TRPT1:p.His172Arg (chr11-64224329-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001033678.4(TRPT1):c.515A>G(p.His172Arg) variant causes a missense change. The variant allele was found at a frequency of 0.17 in 1,613,572 control chromosomes in the GnomAD database, including 24,734 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.16 ( 2307 hom., cov: 33)

Exomes 𝑓: 0.17 ( 22427 hom. )

Consequence

TRPT1
NM_001033678.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.08

Publications

59 publications found

Variant links:

Genes affected

TRPT1 (HGNC:20316): (tRNA phosphotransferase 1) Predicted to enable tRNA 2'-phosphotransferase activity. Predicted to be involved in tRNA splicing, via endonucleolytic cleavage and ligation. Predicted to act upstream of or within regulation of protein kinase activity. [provided by Alliance of Genome Resources, Apr 2022]

TRPT1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0058959126).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPT1	NM_001033678.4 link	c.515A>G	p.His172Arg	missense_variant	Exon 6 of 8	ENST00000317459.11	NP_001028850.2	Q86TN4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPT1	ENST00000317459.11 link	c.515A>G	p.His172Arg	missense_variant	Exon 6 of 8	1	NM_001033678.4	ENSP00000314073.6		Q86TN4-1

Frequencies

GnomAD3 genomes

AF:

0.164

AC:

24887

AN:

152112

Hom.:

2303

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.130

Gnomad AMR

AF:

0.281

Gnomad ASJ

AF:

0.176

Gnomad EAS

AF:

0.189

Gnomad SAS

AF:

0.0886

Gnomad FIN

AF:

0.175

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.173

Gnomad OTH

AF:

0.195

GnomAD2 exomes

AF:

0.178

AC:

44634

AN:

250610

AF XY:

0.173

show subpopulations

Gnomad AFR exome

AF:

0.101

Gnomad AMR exome

AF:

0.305

Gnomad ASJ exome

AF:

0.181

Gnomad EAS exome

AF:

0.187

Gnomad FIN exome

AF:

0.170

Gnomad NFE exome

AF:

0.171

Gnomad OTH exome

AF:

0.188

GnomAD4 exome

AF:

0.171

AC:

249652

AN:

1461342

Hom.:

22427

Cov.:

AF XY:

0.169

AC XY:

122684

AN XY:

726942

show subpopulations

African (AFR)

AF:

0.100

AC:

3354

AN:

33478

American (AMR)

AF:

0.308

AC:

13786

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.178

AC:

4663

AN:

26136

East Asian (EAS)

AF:

0.184

AC:

7318

AN:

39684

South Asian (SAS)

AF:

0.0968

AC:

8346

AN:

86258

European-Finnish (FIN)

AF:

0.170

AC:

8992

AN:

52970

Middle Eastern (MID)

AF:

0.190

AC:

1094

AN:

5768

European-Non Finnish (NFE)

AF:

0.172

AC:

191229

AN:

1111952

Other (OTH)

AF:

0.180

AC:

10870

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

11943

23887

35830

47774

59717

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.164

AC:

24903

AN:

152230

Hom.:

2307

Cov.:

AF XY:

0.166

AC XY:

12344

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.105

AC:

4352

AN:

41546

American (AMR)

AF:

0.281

AC:

4298

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.176

AC:

610

AN:

3472

East Asian (EAS)

AF:

0.188

AC:

976

AN:

5178

South Asian (SAS)

AF:

0.0889

AC:

429

AN:

4826

European-Finnish (FIN)

AF:

0.175

AC:

1850

AN:

10594

Middle Eastern (MID)

AF:

0.190

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.173

AC:

11790

AN:

67998

Other (OTH)

AF:

0.200

AC:

423

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1099

2198

3296

4395

5494

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.170

Hom.:

7022

Bravo

AF:

0.171

TwinsUK

AF:

0.173

AC:

640

ALSPAC

AF:

0.167

AC:

644

ESP6500AA

AF:

0.105

AC:

464

ESP6500EA

AF:

0.173

AC:

1483

ExAC

AF:

0.169

AC:

20564

Asia WGS

AF:

0.152

AC:

527

AN:

3478

EpiCase

AF:

0.174

EpiControl

AF:

0.173

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.015

.;.;.;T;T;T;T

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.44

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.89

D;D;D;D;D;T;T

MetaRNN

Benign

0.0059

T;T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.0

.;L;.;.;L;.;.

PhyloP100

4.1

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.96

N;N;N;N;N;N;N

REVEL

Benign

0.078

Sift

Uncertain

0.0090

D;D;D;T;D;D;T

Sift4G

Benign

0.12

T;T;T;D;T;T;T

Polyphen

0.10

B;.;.;.;B;.;.

Vest4

0.099

MPC

0.27

ClinPred

0.020

GERP RS

2.6

PromoterAI

-0.019

Neutral

(source)

Varity_R

0.15

gMVP

0.55

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

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11-64224329-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over