Variant chrX-101023501-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The ENST00000372936.4(TRMT2B):c.725T>C(p.Ile242Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000227 in 1,208,616 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 98 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., 7 hem., cov: 23)

Exomes 𝑓: 0.00023 ( 0 hom. 91 hem. )

Consequence

TRMT2B
ENST00000372936.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.37

Variant links:

Genes affected

TRMT2B (HGNC:25748): (tRNA methyltransferase 2 homolog B) This gene encodes a homolog of the TRM2 gene in S. cerevisiae. The yeast gene encodes a tRNA methyltransferase that plays a role in tRNA maturation. The yeast protein also has endo-exonuclease activity and may be involved in DNA double strand break repair. Alternative splicing results in multiple transcripts encoding different isoforms. [provided by RefSeq, Nov 2009]

TRMT2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.29414067).

BS2

High Hemizygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRMT2B	NM_024917.6 linkuse as main transcript	c.725T>C	p.Ile242Thr	missense_variant	8/14	ENST00000372936.4	NP_079193.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRMT2B	ENST00000372936.4 linkuse as main transcript	c.725T>C	p.Ile242Thr	missense_variant	8/14	1	NM_024917.6	ENSP00000362027	P1	Q96GJ1-1
TRMT2B	ENST00000372935.5 linkuse as main transcript	c.725T>C	p.Ile242Thr	missense_variant	8/14	1		ENSP00000362026	P1	Q96GJ1-1
TRMT2B	ENST00000545398.5 linkuse as main transcript	c.725T>C	p.Ile242Thr	missense_variant	7/13	1		ENSP00000438134	P1	Q96GJ1-1
TRMT2B	ENST00000372939.5 linkuse as main transcript	c.590T>C	p.Ile197Thr	missense_variant	8/14	1		ENSP00000362030		Q96GJ1-3

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

112304

Hom.:

Cov.:

AF XY:

0.000203

AC XY:

AN XY:

34470

show subpopulations

Gnomad AFR

AF:

0.0000970

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:

0.000263

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000819

AC:

AN:

183124

Hom.:

AF XY:

0.000148

AC XY:

AN XY:

67634

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000625

Gnomad NFE exome

AF:

0.000171

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000234

AC:

257

AN:

1096312

Hom.:

Cov.:

AF XY:

0.000251

AC XY:

AN XY:

361882

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000247

Gnomad4 NFE exome

AF:

0.000300

Gnomad4 OTH exome

AF:

0.0000869

GnomAD4 genome

AF:

0.000151

AC:

AN:

112304

Hom.:

Cov.:

AF XY:

0.000203

AC XY:

AN XY:

34470

show subpopulations

Gnomad4 AFR

AF:

0.0000970

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:

0.000263

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000208

Hom.:

Bravo

AF:

0.000121

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000692

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000446

AC:

ExAC

AF:

0.000132

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

Nov 21, 2022

The c.725T>C (p.I242T) alteration is located in exon 8 (coding exon 6) of the TRMT2B gene. This alteration results from a T to C substitution at nucleotide position 725, causing the isoleucine (I) at amino acid position 242 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

Uncertain

0.45

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

T;.;T;T

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.90

D;D;.;.

M_CAP

Benign

0.070

MetaRNN

Benign

0.29

T;T;T;T

MetaSVM

Benign

-0.55

MutationAssessor

Uncertain

2.6

M;.;M;M

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-4.5

D;D;D;D

REVEL

Benign

0.25

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Uncertain

0.0060

D;D;D;D

Polyphen

0.40

B;D;B;B

Vest4

0.56

MVP

0.38

MPC

0.63

ClinPred

0.59

GERP RS

4.6

Varity_R

0.80

gMVP

0.88

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