Variant chr10-17157774-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004412.7(TRDMT1):c.554A>G(p.Glu185Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000259 in 1,590,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

TRDMT1
NM_004412.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.90

Variant links:

Genes affected

TRDMT1 (HGNC:2977): (tRNA aspartic acid methyltransferase 1) This gene encodes a protein responsible for the methylation of aspartic acid transfer RNA, specifically at the cytosine-38 residue in the anticodon loop. This enzyme also possesses residual DNA-(cytosine-C5) methyltransferase activity. While similar in sequence and structure to DNA cytosine methyltransferases, this gene is distinct and highly conserved in its function among taxa. [provided by RefSeq, Jun 2010]

TRDMT1 links:

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=0.06338474).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRDMT1	NM_004412.7 linkuse as main transcript	c.554A>G	p.Glu185Gly	missense_variant	8/11	ENST00000377799.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRDMT1	ENST00000377799.8 linkuse as main transcript	c.554A>G	p.Glu185Gly	missense_variant	8/11	1	NM_004412.7	P1	O14717-1

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000660

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000370

AC:

AN:

235210

Hom.:

AF XY:

0.000330

AC XY:

AN XY:

127136

show subpopulations

Gnomad AFR exome

AF:

0.0000633

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000548

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00131

Gnomad NFE exome

AF:

0.000497

Gnomad OTH exome

AF:

0.000353

GnomAD4 exome

AF:

0.000263

AC:

378

AN:

1438434

Hom.:

Cov.:

AF XY:

0.000254

AC XY:

181

AN XY:

713584

show subpopulations

Gnomad4 AFR exome

AF:

0.0000307

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000631

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00126

Gnomad4 NFE exome

AF:

0.000259

Gnomad4 OTH exome

AF:

0.000202

GnomAD4 genome

AF:

0.000223

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000660

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000541

Hom.:

Bravo

AF:

0.000174

ExAC

AF:

0.000346

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

Oct 25, 2022

The c.554A>G (p.E185G) alteration is located in exon 8 (coding exon 8) of the TRDMT1 gene. This alteration results from a A to G substitution at nucleotide position 554, causing the glutamic acid (E) at amino acid position 185 to be replaced by a glycine (G). 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

0.089

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.76

D;T

Eigen

Benign

-0.023

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.66

T;T

M_CAP

Pathogenic

0.44

MetaRNN

Benign

0.063

T;T

MetaSVM

Uncertain

0.74

MutationAssessor

Benign

1.9

M;.

MutationTaster

Benign

1.0

D;D;N;N;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.4

N;D

REVEL

Uncertain

0.33

Sift

Benign

0.15

T;D

Sift4G

Benign

0.19

T;T

Polyphen

0.015

B;D

Vest4

0.24

MVP

0.99

MPC

0.017

ClinPred

0.053

GERP RS

5.6

Varity_R

0.30

gMVP

0.51

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