Variant chr10-17157781-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_004412.7(TRDMT1):c.547C>T(p.Leu183=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00178 in 1,559,358 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0093 ( 19 hom., cov: 33)

Exomes 𝑓: 0.00097 ( 19 hom. )

Consequence

TRDMT1
NM_004412.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.531

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 Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 10-17157781-G-A is Benign according to our data. Variant chr10-17157781-G-A is described in ClinVar as [Benign]. Clinvar id is 780850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.531 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00927 (1411/152226) while in subpopulation AFR AF= 0.0326 (1352/41528). AF 95% confidence interval is 0.0311. There are 19 homozygotes in gnomad4. There are 660 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRDMT1	NM_004412.7 linkuse as main transcript	c.547C>T	p.Leu183=	synonymous_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.547C>T	p.Leu183=	synonymous_variant	8/11	1	NM_004412.7	P1	O14717-1

Frequencies

GnomAD3 genomes

AF:

0.00926

AC:

1409

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0326

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00274

AC:

591

AN:

215742

Hom.:

AF XY:

0.00184

AC XY:

215

AN XY:

116996

show subpopulations

Gnomad AFR exome

AF:

0.0350

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000422

Gnomad FIN exome

AF:

0.0000569

Gnomad NFE exome

AF:

0.0000777

Gnomad OTH exome

AF:

0.00117

GnomAD4 exome

AF:

0.000971

AC:

1367

AN:

1407132

Hom.:

Cov.:

AF XY:

0.000846

AC XY:

589

AN XY:

696026

show subpopulations

Gnomad4 AFR exome

AF:

0.0364

Gnomad4 AMR exome

AF:

0.00158

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000632

Gnomad4 FIN exome

AF:

0.0000208

Gnomad4 NFE exome

AF:

0.0000478

Gnomad4 OTH exome

AF:

0.00186

GnomAD4 genome

AF:

0.00927

AC:

1411

AN:

152226

Hom.:

Cov.:

AF XY:

0.00887

AC XY:

660

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0326

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.00405

Hom.:

Bravo

AF:

0.0106

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 14, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

6.1

DANN

Benign

0.65

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