22-20114860-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022727.6(TRMT2A):c.1022A>T(p.Glu341Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 12/21 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.57

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRMT2A	NM_022727.6	c.1022A>T	p.Glu341Val	missense_variant	6/12	ENST00000252136.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRMT2A	ENST00000252136.12	c.1022A>T	p.Glu341Val	missense_variant	6/12	1	NM_022727.6	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 27, 2022

The c.1022A>T (p.E341V) alteration is located in exon 6 (coding exon 6) of the TRMT2A gene. This alteration results from a A to T substitution at nucleotide position 1022, causing the glutamic acid (E) at amino acid position 341 to be replaced by a valine (V). 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	0.13
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.30
Cadd	Benign	23
Dann	Benign	0.97
DEOGEN2	Benign	0.25	T;T;.;T
Eigen	Benign	-0.060
Eigen_PC	Benign	-0.0077
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.076	D
MetaRNN	Uncertain	0.51	D;D;D;D
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	2.0	M;M;M;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-5.2	D;D;D;D
REVEL	Benign	0.21
Sift	Benign	0.033	D;D;D;D
Sift4G	Uncertain	0.017	D;D;D;D
Polyphen		0.052	B;B;B;B
Vest4		0.71
MutPred		0.58		Loss of disorder (P = 0.0096);Loss of disorder (P = 0.0096);Loss of disorder (P = 0.0096);Loss of disorder (P = 0.0096);
MVP		0.33
MPC		0.15
ClinPred		0.95	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.43
gMVP		0.76

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-20102383;