22-20116203-C-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_022727.6(TRMT2A):c.434G>A(p.Arg145Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000645 in 1,612,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000068 ( 0 hom. )
Consequence
TRMT2A
NM_022727.6 missense
NM_022727.6 missense
Scores
5
13
Clinical Significance
Conservation
PhyloP100: 5.62
Genes affected
TRMT2A (HGNC:24974): (tRNA methyltransferase 2 homolog A) The protein encoded by this gene is of unknown function. However, it is orthologous to the mouse Trmt2a gene and contains an RNA methyltransferase domain. Expression of this gene varies during the cell cycle, with aberrant expression being a possible biomarker in certain breast cancers. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]
RANBP1 (HGNC:9847): (RAN binding protein 1) This gene encodes a protein that forms a complex with Ras-related nuclear protein (Ran) and metabolizes guanoside triphosphate (GTP). This complex participates in the regulation of the cell cycle by controlling transport of proteins and nucleic acids into the nucleus. There are multiple pseudogenes for this gene on chromosomes 9, 12, 17, and X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
Genome browser will be placed here
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=0.21808577).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRMT2A | NM_022727.6 | c.434G>A | p.Arg145Gln | missense_variant | 2/12 | ENST00000252136.12 | |
RANBP1 | NM_001278639.2 | c.19C>T | p.Arg7Trp | missense_variant | 1/6 | ENST00000430524.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRMT2A | ENST00000252136.12 | c.434G>A | p.Arg145Gln | missense_variant | 2/12 | 1 | NM_022727.6 | P1 | |
RANBP1 | ENST00000430524.6 | c.19C>T | p.Arg7Trp | missense_variant | 1/6 | 3 | NM_001278639.2 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152266Hom.: 0 Cov.: 33
GnomAD3 genomes
AF:
AC:
4
AN:
152266
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 249774Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135450
GnomAD3 exomes
AF:
AC:
5
AN:
249774
Hom.:
AF XY:
AC XY:
3
AN XY:
135450
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000685 AC: 100AN: 1460662Hom.: 0 Cov.: 33 AF XY: 0.0000647 AC XY: 47AN XY: 726642
GnomAD4 exome
AF:
AC:
100
AN:
1460662
Hom.:
Cov.:
33
AF XY:
AC XY:
47
AN XY:
726642
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152266Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74392
GnomAD4 genome
AF:
AC:
4
AN:
152266
Hom.:
Cov.:
33
AF XY:
AC XY:
3
AN XY:
74392
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
1
EpiCase
AF:
EpiControl
AF:
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 | Feb 27, 2024 | The c.434G>A (p.R145Q) alteration is located in exon 2 (coding exon 2) of the TRMT2A gene. This alteration results from a G to A substitution at nucleotide position 434, causing the arginine (R) at amino acid position 145 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Benign
T;T;T;T
Polyphen
B;B;.;B
Vest4
MutPred
Loss of methylation at R145 (P = 0.0398);Loss of methylation at R145 (P = 0.0398);Loss of methylation at R145 (P = 0.0398);Loss of methylation at R145 (P = 0.0398);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at