Variant chr1-100133284-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_019083.3(TRMT13):c.116G>C(p.Arg39Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

TRMT13
NM_019083.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.70

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21166846).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRMT13	NM_019083.3 linkuse as main transcript	c.116G>C	p.Arg39Thr	missense_variant	1/11	ENST00000370141.8	NP_061956.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRMT13	ENST00000370141.8 linkuse as main transcript	c.116G>C	p.Arg39Thr	missense_variant	1/11	1	NM_019083.3	ENSP00000359160	P1	Q9NUP7-1
TRMT13	ENST00000370139.1 linkuse as main transcript	c.23G>C	p.Arg8Thr	missense_variant	1/6	3		ENSP00000359158
TRMT13	ENST00000370143.5 linkuse as main transcript	c.116G>C	p.Arg39Thr	missense_variant	1/5	3		ENSP00000359162
TRMT13	ENST00000482437.5 linkuse as main transcript	c.116G>C	p.Arg39Thr	missense_variant, NMD_transcript_variant	1/8	2		ENSP00000432616		Q9NUP7-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 04, 2022

The c.116G>C (p.R39T) alteration is located in exon 1 (coding exon 1) of the TRMT13 gene. This alteration results from a G to C substitution at nucleotide position 116, causing the arginine (R) at amino acid position 39 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.063

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.019

.;T;.

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.048

LIST_S2

Uncertain

0.89

D;D;D

M_CAP

Benign

0.026

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

.;L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.14

Sift

Benign

0.28

T;T;T

Sift4G

Benign

0.52

T;T;T

Polyphen

0.42

.;B;.

Vest4

0.57

MVP

0.52

MPC

0.32

ClinPred

0.19

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.18

gMVP

0.49

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

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