Variant 22-20116122-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_022727.6(TRMT2A):c.515T>C(p.Val172Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000225 in 1,612,498 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

TRMT2A
NM_022727.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.78

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:

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]

RANBP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
TRMT2A	NM_022727.6 linkuse as main transcript	c.515T>C	p.Val172Ala	missense_variant	2/12	ENST00000252136.12	NP_073564.3
RANBP1	NM_001278639.2 linkuse as main transcript	c.-63A>G		5_prime_UTR_variant	1/6	ENST00000430524.6	NP_001265568.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRMT2A	ENST00000252136.12 linkuse as main transcript	c.515T>C	p.Val172Ala	missense_variant	2/12	1	NM_022727.6	ENSP00000252136	P1	Q8IZ69-1
RANBP1	ENST00000430524.6 linkuse as main transcript	c.-63A>G		5_prime_UTR_variant	1/6	3	NM_001278639.2	ENSP00000401564	A2

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152272

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000168

AC:

AN:

249864

Hom.:

AF XY:

0.000163

AC XY:

AN XY:

135290

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000338

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000231

AC:

338

AN:

1460226

Hom.:

Cov.:

AF XY:

0.000208

AC XY:

151

AN XY:

726242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000286

Gnomad4 NFE exome

AF:

0.000275

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.000164

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000315

Hom.:

Bravo

AF:

0.000132

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.000222

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

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

Mar 14, 2023

The c.515T>C (p.V172A) alteration is located in exon 2 (coding exon 2) of the TRMT2A gene. This alteration results from a T to C substitution at nucleotide position 515, causing the valine (V) at amino acid position 172 to be replaced by an alanine (A). 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

0.68

BayesDel_addAF

Benign

-0.045

BayesDel_noAF

Uncertain

0.010

CADD

Uncertain

DANN

Benign

0.95

DEOGEN2

Benign

0.10

T;T;.;T

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.83

.;T;T;T

M_CAP

Benign

0.046

MetaRNN

Uncertain

0.63

D;D;D;D

MetaSVM

Benign

-0.56

MutationAssessor

Uncertain

2.4

M;M;M;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-2.7

D;D;D;D

REVEL

Uncertain

0.33

Sift

Benign

0.10

T;T;T;T

Sift4G

Benign

0.094

T;T;T;T

Polyphen

0.74

P;P;.;P

Vest4

0.83

MVP

0.54

MPC

0.26

ClinPred

0.23

GERP RS

5.3

Varity_R

0.26

gMVP

0.78

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