Genetic Variant TRPT1:p.Gly131Asp (chr11-64224653-C-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001033678.4(TRPT1):c.392G>A(p.Gly131Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000143 in 1,607,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

TRPT1
NM_001033678.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.88

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.908

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033678.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRPT1	NM_001033678.4	MANE Select	c.392G>A	p.Gly131Asp	missense	Exon 5 of 8	NP_001028850.2	Q86TN4-1
TRPT1	NM_001160389.2		c.398G>A	p.Gly133Asp	missense	Exon 5 of 8	NP_001153861.1	Q86TN4-4
TRPT1	NM_001160393.1		c.392G>A	p.Gly131Asp	missense	Exon 4 of 7	NP_001153865.1	Q86TN4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRPT1	ENST00000317459.11	TSL:1 MANE Select	c.392G>A	p.Gly131Asp	missense	Exon 5 of 8	ENSP00000314073.6	Q86TN4-1
TRPT1	ENST00000394547.7	TSL:1	c.245G>A	p.Gly82Asp	missense	Exon 4 of 7	ENSP00000378051.3	Q86TN4-2
TRPT1	ENST00000394546.6	TSL:5	c.398G>A	p.Gly133Asp	missense	Exon 5 of 8	ENSP00000378050.2	Q86TN4-4

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000122

AC:

AN:

244946

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000294

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000124

AC:

AN:

1455678

Hom.:

Cov.:

AF XY:

0.00000829

AC XY:

AN XY:

723780

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

33404

American (AMR)

AF:

0.0000226

AC:

AN:

44266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25578

East Asian (EAS)

AF:

0.00

AC:

AN:

39666

South Asian (SAS)

AF:

0.00

AC:

AN:

85354

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53082

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.00000902

AC:

AN:

1108426

Other (OTH)

AF:

0.0000499

AC:

AN:

60168

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41448

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000416

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Pathogenic

0.27

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.42

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.83

M_CAP

Uncertain

0.26

MetaRNN

Pathogenic

0.91

MetaSVM

Uncertain

0.49

MutationAssessor

Pathogenic

4.4

PhyloP100

4.9

PrimateAI

Uncertain

0.65

PROVEAN

Pathogenic

-6.5

REVEL

Pathogenic

0.68

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.92

MVP

0.92

MPC

0.95

ClinPred

0.99

GERP RS

4.4

PromoterAI

-0.0073

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.95

gMVP

0.98

Mutation Taster

=24/76

disease causing

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over