X-101020552-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_024917.6(TRMT2B):​c.1103G>A​(p.Arg368Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000579 in 1,209,350 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 1 hem., cov: 23)
Exomes 𝑓: 0.0000027 ( 0 hom. 1 hem. )

Consequence

TRMT2B
NM_024917.6 missense

Scores

17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.40
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.063755095).
BP6
Variant X-101020552-C-T is Benign according to our data. Variant chrX-101020552-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3461881.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRMT2BNM_024917.6 linkc.1103G>A p.Arg368Gln missense_variant Exon 11 of 14 ENST00000372936.4 NP_079193.2 Q96GJ1-1A0A024RCF5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRMT2BENST00000372936.4 linkc.1103G>A p.Arg368Gln missense_variant Exon 11 of 14 1 NM_024917.6 ENSP00000362027.3 Q96GJ1-1
TRMT2BENST00000372935.5 linkc.1103G>A p.Arg368Gln missense_variant Exon 11 of 14 1 ENSP00000362026.1 Q96GJ1-1
TRMT2BENST00000545398.5 linkc.1103G>A p.Arg368Gln missense_variant Exon 10 of 13 1 ENSP00000438134.1 Q96GJ1-1
TRMT2BENST00000372939.5 linkc.968G>A p.Arg323Gln missense_variant Exon 11 of 14 1 ENSP00000362030.1 Q96GJ1-3

Frequencies

GnomAD3 genomes
AF:
0.0000357
AC:
4
AN:
112122
Hom.:
0
Cov.:
23
AF XY:
0.0000292
AC XY:
1
AN XY:
34292
show subpopulations
Gnomad AFR
AF:
0.000129
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000273
AC:
3
AN:
1097228
Hom.:
0
Cov.:
29
AF XY:
0.00000276
AC XY:
1
AN XY:
362602
show subpopulations
Gnomad4 AFR exome
AF:
0.0000379
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:
0.00
Gnomad4 NFE exome
AF:
0.00000238
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000357
AC:
4
AN:
112122
Hom.:
0
Cov.:
23
AF XY:
0.0000292
AC XY:
1
AN XY:
34292
show subpopulations
Gnomad4 AFR
AF:
0.000129
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Aug 27, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.066
BayesDel_addAF
Benign
-0.53
T
BayesDel_noAF
Benign
-1.0
CADD
Benign
6.0
DANN
Benign
0.26
DEOGEN2
Benign
0.054
T;.;T;T
FATHMM_MKL
Benign
0.00083
N
LIST_S2
Benign
0.62
T;T;.;.
M_CAP
Benign
0.0031
T
MetaRNN
Benign
0.064
T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
-0.41
N;.;N;N
PrimateAI
Benign
0.21
T
PROVEAN
Benign
-0.83
N;N;N;N
REVEL
Benign
0.059
Sift
Benign
0.90
T;T;T;T
Sift4G
Benign
1.0
T;T;T;T
Polyphen
0.0010
B;B;B;B
Vest4
0.075
MutPred
0.54
Loss of methylation at R368 (P = 0.176);.;Loss of methylation at R368 (P = 0.176);Loss of methylation at R368 (P = 0.176);
MVP
0.35
MPC
0.34
ClinPred
0.019
T
GERP RS
0.75
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.042
gMVP
0.16

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs1249351585; hg19: chrX-100275541; API