Variant X-101021223-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_024917.6(TRMT2B):c.944G>T(p.Arg315Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,209,749 control chromosomes in the GnomAD database, including 1 homozygotes. There are 36 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 0.00054 ( 0 hom., 24 hem., cov: 23)

Exomes 𝑓: 0.000057 ( 1 hom. 12 hem. )

Consequence

TRMT2B
NM_024917.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.375

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:

TRMT2B (HGNC:):

TRMT2B links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09814417).

BS2

High Hemizygotes in GnomAd4 at 24 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRMT2B	NM_024917.6 linkuse as main transcript	c.944G>T	p.Arg315Leu	missense_variant	10/14	ENST00000372936.4	NP_079193.2	Q96GJ1-1A0A024RCF5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TRMT2B	ENST00000372936.4 linkuse as main transcript	c.944G>T	p.Arg315Leu	missense_variant	10/14	1	NM_024917.6	ENSP00000362027.3	Q96GJ1-1
TRMT2B	ENST00000372935.5 linkuse as main transcript	c.944G>T	p.Arg315Leu	missense_variant	10/14	1		ENSP00000362026.1	Q96GJ1-1
TRMT2B	ENST00000545398.5 linkuse as main transcript	c.944G>T	p.Arg315Leu	missense_variant	9/13	1		ENSP00000438134.1	Q96GJ1-1
TRMT2B	ENST00000372939.5 linkuse as main transcript	c.809G>T	p.Arg270Leu	missense_variant	10/14	1		ENSP00000362030.1	Q96GJ1-3

Frequencies

GnomAD3 genomes

AF:

0.000536

AC:

AN:

111860

Hom.:

Cov.:

AF XY:

0.000705

AC XY:

AN XY:

34022

show subpopulations

Gnomad AFR

AF:

0.000877

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00307

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:

0.00

Gnomad OTH

AF:

0.000669

GnomAD3 exomes

AF:

0.0000928

AC:

AN:

183172

Hom.:

AF XY:

0.0000591

AC XY:

AN XY:

67724

show subpopulations

Gnomad AFR exome

AF:

0.000760

Gnomad AMR exome

AF:

0.000182

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000524

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.0000574

AC:

AN:

1097836

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

363192

show subpopulations

Gnomad4 AFR exome

AF:

0.00121

Gnomad4 AMR exome

AF:

0.000483

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000369

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.000239

GnomAD4 genome

AF:

0.000536

AC:

AN:

111913

Hom.:

Cov.:

AF XY:

0.000704

AC XY:

AN XY:

34085

show subpopulations

Gnomad4 AFR

AF:

0.000875

Gnomad4 AMR

AF:

0.00306

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000661

Alfa

AF:

0.0000463

Hom.:

Bravo

AF:

0.00114

ESP6500AA

AF:

0.000782

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000659

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 13, 2024

The c.944G>T (p.R315L) alteration is located in exon 10 (coding exon 8) of the TRMT2B gene. This alteration results from a G to T substitution at nucleotide position 944, causing the arginine (R) at amino acid position 315 to be replaced by a leucine (L). 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

0.52

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

T;.;T;T

FATHMM_MKL

Benign

0.67

LIST_S2

Uncertain

0.91

D;D;.;.

M_CAP

Pathogenic

0.53

MetaRNN

Benign

0.098

T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Pathogenic

3.2

M;.;M;M

PrimateAI

Benign

0.18

PROVEAN

Pathogenic

-6.4

D;D;D;D

REVEL

Benign

0.26

Sift

Uncertain

0.0020

D;D;D;D

Sift4G

Uncertain

0.0090

D;D;D;D

Polyphen

0.61

P;D;P;P

Vest4

0.26

MVP

0.33

MPC

1.1

ClinPred

0.43

GERP RS

1.1

Varity_R

0.72

gMVP

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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