Variant 19-13105301-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001136035.4(TRMT1):c.1799G>A(p.Arg600Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000752 in 1,614,010 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0033 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00048 ( 2 hom. )

Consequence

TRMT1
NM_001136035.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.306

Variant links:

Genes affected

TRMT1 (HGNC:25980): (tRNA methyltransferase 1) This gene encodes a tRNA-modifying enzyme that acts as a dimethyltransferase, modifying a single guanine residue at position 26 of the tRNA. The encoded enzyme has both mono- and dimethylase activity when exogenously expressed, and uses S-adenosyl methionine as a methyl donor. The C-terminal region of the encoded protein has both a zinc finger motif, and an arginine/proline-rich region. Mutations in this gene have been implicated in autosomal recessive intellectual disorder (ARID). Alternative splicing results in multiple transcript variants encoding different isoforms. There is a pseudogene of this gene on the X chromosome. [provided by RefSeq, May 2017]

TRMT1 links:

TRMT1 (HGNC:):

TRMT1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0056091547).

BP6

Variant 19-13105301-C-T is Benign according to our data. Variant chr19-13105301-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3025195.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00334 (508/152320) while in subpopulation AFR AF= 0.0109 (452/41572). AF 95% confidence interval is 0.01. There are 2 homozygotes in gnomad4. There are 244 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRMT1	NM_001136035.4 linkuse as main transcript	c.1799G>A	p.Arg600Gln	missense_variant	16/17	ENST00000357720.9	NP_001129507.1	Q9NXH9-1A0A024R7I5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRMT1	ENST00000357720.9 linkuse as main transcript	c.1799G>A	p.Arg600Gln	missense_variant	16/17	2	NM_001136035.4	ENSP00000350352.4		Q9NXH9-1

Frequencies

GnomAD3 genomes

AF:

0.00332

AC:

505

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0108

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00107

AC:

268

AN:

251154

Hom.:

AF XY:

0.000921

AC XY:

125

AN XY:

135790

show subpopulations

Gnomad AFR exome

AF:

0.0107

Gnomad AMR exome

AF:

0.00150

Gnomad ASJ exome

AF:

0.00139

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.000979

GnomAD4 exome

AF:

0.000483

AC:

706

AN:

1461690

Hom.:

Cov.:

AF XY:

0.000459

AC XY:

334

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.0117

Gnomad4 AMR exome

AF:

0.00150

Gnomad4 ASJ exome

AF:

0.000995

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.0000563

Gnomad4 NFE exome

AF:

0.000125

Gnomad4 OTH exome

AF:

0.00101

GnomAD4 genome

AF:

0.00334

AC:

508

AN:

152320

Hom.:

Cov.:

AF XY:

0.00328

AC XY:

244

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0109

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00120

Hom.:

Bravo

AF:

0.00369

ESP6500AA

AF:

0.0107

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00116

AC:

141

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000296

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2024

TRMT1: BP4, BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.021

T;T;.;T

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.69

T;.;T;.

MetaRNN

Benign

0.0056

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L;.;L

PrimateAI

Benign

0.29

PROVEAN

Benign

0.28

N;N;N;.

REVEL

Benign

0.026

Sift

Benign

0.22

T;T;T;.

Sift4G

Benign

0.25

T;T;T;T

Polyphen

0.0050

B;B;B;B

Vest4

0.23

MVP

0.37

MPC

0.16

ClinPred

0.013

GERP RS

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.020

gMVP

0.11

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over