Variant 10-17157748-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_004412.7(TRDMT1):c.580C>A(p.Pro194Thr) 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. 16/21 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: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRDMT1
NM_004412.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.849

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:

TRDMT1 (HGNC:):

TRDMT1 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=0.104349226).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRDMT1	NM_004412.7 linkuse as main transcript	c.580C>A	p.Pro194Thr	missense_variant	8/11	ENST00000377799.8	NP_004403.1	O14717-1Q6ICS7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRDMT1	ENST00000377799.8 linkuse as main transcript	c.580C>A	p.Pro194Thr	missense_variant	8/11	1	NM_004412.7	ENSP00000367030.3		O14717-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1451706

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721320

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:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Aug 20, 2024

The c.580C>A (p.P194T) alteration is located in exon 8 (coding exon 8) of the TRDMT1 gene. This alteration results from a C to A substitution at nucleotide position 580, causing the proline (P) at amino acid position 194 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

0.070

BayesDel_addAF

Benign

-0.050

BayesDel_noAF

Benign

-0.31

CADD

Benign

6.4

DANN

Benign

0.88

DEOGEN2

Uncertain

0.60

D;T

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.039

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.2

L;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.20

Sift

Benign

0.11

T;T

Sift4G

Benign

0.38

T;T

Polyphen

0.0010

B;P

Vest4

0.12

MutPred

0.45

Loss of disorder (P = 0.0561);.;

MVP

0.92

MPC

0.017

ClinPred

0.16

GERP RS

3.1

Varity_R

0.057

gMVP

0.40

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over