Variant 1-100133310-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_019083.3(TRMT13):c.142G>A(p.Ala48Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.839 in 1,612,804 control chromosomes in the GnomAD database, including 574,372 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A48V) has been classified as Benign.

Frequency

Genomes: 𝑓 0.75 ( 45051 hom., cov: 30)

Exomes 𝑓: 0.85 ( 529321 hom. )

Consequence

TRMT13
NM_019083.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.02

Variant links:

Genes affected

TRMT13 (HGNC:25502): (tRNA methyltransferase 13 homolog) Predicted to enable tRNA methyltransferase activity. Predicted to be involved in tRNA methylation. [provided by Alliance of Genome Resources, Apr 2022]

TRMT13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.7824184E-7).

BP6

Variant 1-100133310-G-A is Benign according to our data. Variant chr1-100133310-G-A is described in ClinVar as [Benign]. Clinvar id is 1233160.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRMT13	NM_019083.3 linkuse as main transcript	c.142G>A	p.Ala48Thr	missense_variant	1/11	ENST00000370141.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRMT13	ENST00000370141.8 linkuse as main transcript	c.142G>A	p.Ala48Thr	missense_variant	1/11	1	NM_019083.3	P1	Q9NUP7-1
TRMT13	ENST00000370139.1 linkuse as main transcript	c.49G>A	p.Ala17Thr	missense_variant	1/6	3
TRMT13	ENST00000370143.5 linkuse as main transcript	c.142G>A	p.Ala48Thr	missense_variant	1/5	3
TRMT13	ENST00000482437.5 linkuse as main transcript	c.142G>A	p.Ala48Thr	missense_variant, NMD_transcript_variant	1/8	2			Q9NUP7-2

Frequencies

GnomAD3 genomes

AF:

0.748

AC:

113325

AN:

151484

Hom.:

45038

Cov.:

show subpopulations

Gnomad AFR

AF:

0.449

Gnomad AMI

AF:

0.806

Gnomad AMR

AF:

0.852

Gnomad ASJ

AF:

0.890

Gnomad EAS

AF:

0.946

Gnomad SAS

AF:

0.896

Gnomad FIN

AF:

0.886

Gnomad MID

AF:

0.852

Gnomad NFE

AF:

0.850

Gnomad OTH

AF:

0.783

GnomAD3 exomes

AF:

0.851

AC:

212751

AN:

250012

Hom.:

92102

AF XY:

0.857

AC XY:

115792

AN XY:

135122

show subpopulations

Gnomad AFR exome

AF:

0.441

Gnomad AMR exome

AF:

0.921

Gnomad ASJ exome

AF:

0.890

Gnomad EAS exome

AF:

0.958

Gnomad SAS exome

AF:

0.894

Gnomad FIN exome

AF:

0.884

Gnomad NFE exome

AF:

0.849

Gnomad OTH exome

AF:

0.856

GnomAD4 exome

AF:

0.848

AC:

1239556

AN:

1461200

Hom.:

529321

Cov.:

AF XY:

0.851

AC XY:

618462

AN XY:

726864

show subpopulations

Gnomad4 AFR exome

AF:

0.435

Gnomad4 AMR exome

AF:

0.915

Gnomad4 ASJ exome

AF:

0.889

Gnomad4 EAS exome

AF:

0.945

Gnomad4 SAS exome

AF:

0.894

Gnomad4 FIN exome

AF:

0.881

Gnomad4 NFE exome

AF:

0.849

Gnomad4 OTH exome

AF:

0.840

GnomAD4 genome

AF:

0.748

AC:

113365

AN:

151604

Hom.:

45051

Cov.:

AF XY:

0.754

AC XY:

55857

AN XY:

74054

show subpopulations

Gnomad4 AFR

AF:

0.448

Gnomad4 AMR

AF:

0.852

Gnomad4 ASJ

AF:

0.890

Gnomad4 EAS

AF:

0.946

Gnomad4 SAS

AF:

0.896

Gnomad4 FIN

AF:

0.886

Gnomad4 NFE

AF:

0.850

Gnomad4 OTH

AF:

0.786

Alfa

AF:

0.834

Hom.:

83654

Bravo

AF:

0.734

TwinsUK

AF:

0.849

AC:

3148

ALSPAC

AF:

0.854

AC:

3292

ESP6500AA

AF:

0.457

AC:

2012

ESP6500EA

AF:

0.845

AC:

7271

ExAC

AF:

0.838

AC:

101741

Asia WGS

AF:

0.868

AC:

3018

AN:

3478

EpiCase

AF:

0.850

EpiControl

AF:

0.848

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.51

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.078

LIST_S2

Benign

0.70

T;T;T

MetaRNN

Benign

5.8e-7

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.93

P;P;P

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.85

N;N;N

REVEL

Benign

0.015

Sift

Benign

0.28

T;T;T

Sift4G

Benign

0.33

T;T;T

Polyphen

0.20

.;B;.

Vest4

0.10

MPC

0.17

ClinPred

0.030

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.37

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