Genetic Variant TRPT1:c.327+4G>T (chr11-64224797-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001160389.2(TRPT1):c.331G>T(p.Gly111Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,232 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G111R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TRPT1
NM_001160389.2 missense, splice_region

Scores

Splicing: ADA: 0.00003951

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0750

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21931571).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001160389.2. 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.327+4G>T		splice_region intron	N/A	NP_001028850.2	Q86TN4-1
TRPT1	NM_001160389.2		c.331G>T	p.Gly111Trp	missense splice_region	Exon 4 of 8	NP_001153861.1	Q86TN4-4
TRPT1	NM_001160393.1		c.327+4G>T		splice_region intron	N/A	NP_001153865.1	Q86TN4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRPT1	ENST00000317459.11	TSL:1 MANE Select	c.327+4G>T		splice_region intron	N/A	ENSP00000314073.6	Q86TN4-1
TRPT1	ENST00000394547.7	TSL:1	c.180+4G>T		splice_region intron	N/A	ENSP00000378051.3	Q86TN4-2
TRPT1	ENST00000394546.6	TSL:5	c.331G>T	p.Gly111Trp	missense splice_region	Exon 4 of 8	ENSP00000378050.2	Q86TN4-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461232

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726858

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.00

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53180

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111710

Other (OTH)

AF:

0.00

AC:

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

5.8

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.022

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.34

M_CAP

Benign

0.028

MetaRNN

Benign

0.22

MetaSVM

Benign

-1.0

PhyloP100

-0.075

PROVEAN

Benign

-1.0

REVEL

Benign

0.083

Sift

Uncertain

0.015

Sift4G

Uncertain

0.018

Vest4

0.43

MutPred

0.56

Gain of catalytic residue at G111 (P = 0.0366)

MVP

0.072

MPC

0.56

ClinPred

0.41

GERP RS

-0.35

PromoterAI

0.0085

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.49

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000040

dbscSNV1_RF

Benign

0.042

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over