Variant 22-20113212-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022727.6(TRMT2A):c.1455C>A(p.His485Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000563 in 1,421,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

TRMT2A
NM_022727.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.63

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]

TRMT2A links:

TRMT2A (HGNC:):

TRMT2A links:

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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=0.22967744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRMT2A	NM_022727.6 linkuse as main transcript	c.1455C>A	p.His485Gln	missense_variant	10/12	ENST00000252136.12	NP_073564.3	Q8IZ69-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRMT2A	ENST00000252136.12 linkuse as main transcript	c.1455C>A	p.His485Gln	missense_variant	10/12	1	NM_022727.6	ENSP00000252136.7		Q8IZ69-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000139

AC:

AN:

215756

Hom.:

AF XY:

0.0000173

AC XY:

AN XY:

115694

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000297

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000192

GnomAD4 exome

AF:

0.00000563

AC:

AN:

1421652

Hom.:

Cov.:

AF XY:

0.00000426

AC XY:

AN XY:

703514

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000342

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

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

Nov 25, 2024

The c.1455C>A (p.H485Q) alteration is located in exon 10 (coding exon 10) of the TRMT2A gene. This alteration results from a C to A substitution at nucleotide position 1455, causing the histidine (H) at amino acid position 485 to be replaced by a glutamine (Q). 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

0.21

BayesDel_addAF

Benign

-0.099

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.24

T;T;T;.;T

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.071

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

.;D;D;D;D

M_CAP

Benign

0.017

MetaRNN

Benign

0.23

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L;.;L;.

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.1

D;D;D;D;D

REVEL

Benign

0.12

Sift

Benign

0.28

T;T;T;T;T

Sift4G

Benign

0.17

T;T;T;T;T

Polyphen

0.048

B;B;.;B;B

Vest4

0.75

MutPred

0.38

.;.;.;.;Gain of sheet (P = 0.0827);

MVP

0.25

MPC

0.26

ClinPred

0.32

GERP RS

4.3

Varity_R

0.31

gMVP

0.72

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over