Menu
GeneBe

22-20112622-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_022727.6(TRMT2A):c.1819C>A(p.Pro607Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

TRMT2A
NM_022727.6 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0300
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.051425487).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TRMT2ANM_022727.6 linkuse as main transcriptc.1819C>A p.Pro607Thr missense_variant 12/12 ENST00000252136.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TRMT2AENST00000252136.12 linkuse as main transcriptc.1819C>A p.Pro607Thr missense_variant 12/121 NM_022727.6 P1Q8IZ69-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

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 submitterclinical testingAmbry GeneticsNov 18, 2023The c.1819C>A (p.P607T) alteration is located in exon 12 (coding exon 12) of the TRMT2A gene. This alteration results from a C to A substitution at nucleotide position 1819, causing the proline (P) at amino acid position 607 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
Benign
0.061
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.57
Cadd
Benign
2.3
Dann
Benign
0.66
DEOGEN2
Benign
0.018
T;T;T;T
Eigen
Benign
-0.93
Eigen_PC
Benign
-0.88
FATHMM_MKL
Benign
0.43
N
M_CAP
Benign
0.0056
T
MetaRNN
Benign
0.051
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.46
N;N;.;.
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-0.090
N;N;N;N
REVEL
Benign
0.038
Sift
Benign
0.24
T;T;T;T
Sift4G
Benign
0.89
T;T;T;T
Polyphen
0.0030
B;B;.;B
Vest4
0.075
MutPred
0.24
.;.;.;Gain of phosphorylation at P625 (P = 0.0238);
MVP
0.085
MPC
0.12
ClinPred
0.036
T
GERP RS
3.9
Varity_R
0.077
gMVP
0.36

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-20100145; API