X-101037001-C-G

Variant summary

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

The NM_024917.6(TRMT2B):​c.511G>C​(p.Val171Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000128 in 1,097,401 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)
Exomes 𝑓: 0.000013 ( 0 hom. 8 hem. )

Consequence

TRMT2B
NM_024917.6 missense

Scores

1
6
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.80
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=0.10104212).
BS2
High Hemizygotes in GnomAdExome4 at 8 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRMT2BNM_024917.6 linkc.511G>C p.Val171Leu missense_variant Exon 6 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.511G>C p.Val171Leu missense_variant Exon 6 of 14 1 NM_024917.6 ENSP00000362027.3 Q96GJ1-1

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD3 exomes
AF:
0.0000273
AC:
5
AN:
183293
Hom.:
0
AF XY:
0.0000295
AC XY:
2
AN XY:
67755
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000144
Gnomad SAS exome
AF:
0.000105
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000221
GnomAD4 exome
AF:
0.0000128
AC:
14
AN:
1097401
Hom.:
0
Cov.:
29
AF XY:
0.0000221
AC XY:
8
AN XY:
362769
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000232
Gnomad4 SAS exome
AF:
0.0000370
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000238
Gnomad4 OTH exome
AF:
0.0000651
GnomAD4 genome
Cov.:
23
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000302
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 12, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.511G>C (p.V171L) alteration is located in exon 6 (coding exon 4) of the TRMT2B gene. This alteration results from a G to C substitution at nucleotide position 511, causing the valine (V) at amino acid position 171 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
Pathogenic
0.66
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
18
DANN
Benign
0.97
DEOGEN2
Benign
0.33
T;.;T;T
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Uncertain
0.87
D;D;.;.
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.10
T;T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Uncertain
2.5
M;.;M;M
PrimateAI
Uncertain
0.63
T
PROVEAN
Uncertain
-2.4
N;N;N;N
REVEL
Benign
0.16
Sift
Benign
0.047
D;D;D;D
Sift4G
Uncertain
0.051
T;D;T;T
Polyphen
0.50
P;P;P;P
Vest4
0.13
MutPred
0.36
Loss of methylation at K169 (P = 0.0653);.;Loss of methylation at K169 (P = 0.0653);Loss of methylation at K169 (P = 0.0653);
MVP
0.54
MPC
0.42
ClinPred
0.15
T
GERP RS
2.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.21
gMVP
0.70

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: rs766602015; hg19: chrX-100291990; API