Genetic Variant TRDMT1:c.1075+2160T>C (chr10-17151347-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001351220.2(TRDMT1):c.*694T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 984,470 control chromosomes in the GnomAD database, including 139,652 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.52 ( 20822 hom., cov: 32)

Exomes 𝑓: 0.53 ( 118830 hom. )

Consequence

TRDMT1
NM_001351220.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.10

Publications

22 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001351220.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TRDMT1	NM_004412.7	MANE Select	c.1075+2160T>C	intron	N/A	NP_004403.1	O14717-1
TRDMT1	NM_001351220.2		c.*694T>C	3_prime_UTR	Exon 11 of 11	NP_001338149.1
TRDMT1	NM_001351222.2		c.*694T>C	3_prime_UTR	Exon 12 of 12	NP_001338151.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TRDMT1	ENST00000377799.8	TSL:1 MANE Select	c.1075+2160T>C	intron	N/A	ENSP00000367030.3	O14717-1
TRDMT1	ENST00000354631.7	TSL:1	n.*1095+2160T>C	intron	N/A	ENSP00000346652.3	Q7Z3E4
TRDMT1	ENST00000929578.1		c.1096+2160T>C	intron	N/A	ENSP00000599637.1

Frequencies

GnomAD3 genomes

AF:

0.521

AC:

79184

AN:

151924

Hom.:

20803

Cov.:

show subpopulations

Gnomad AFR

AF:

0.524

Gnomad AMI

AF:

0.291

Gnomad AMR

AF:

0.438

Gnomad ASJ

AF:

0.579

Gnomad EAS

AF:

0.488

Gnomad SAS

AF:

0.570

Gnomad FIN

AF:

0.550

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.534

Gnomad OTH

AF:

0.507

GnomAD4 exome

AF:

0.534

AC:

444812

AN:

832428

Hom.:

118830

Cov.:

AF XY:

0.535

AC XY:

205671

AN XY:

384410

show subpopulations

African (AFR)

AF:

0.519

AC:

8184

AN:

15776

American (AMR)

AF:

0.409

AC:

402

AN:

982

Ashkenazi Jewish (ASJ)

AF:

0.615

AC:

3168

AN:

5148

East Asian (EAS)

AF:

0.500

AC:

1810

AN:

3622

South Asian (SAS)

AF:

0.584

AC:

9611

AN:

16448

European-Finnish (FIN)

AF:

0.533

AC:

147

AN:

276

Middle Eastern (MID)

AF:

0.572

AC:

927

AN:

1622

European-Non Finnish (NFE)

AF:

0.533

AC:

405885

AN:

761276

Other (OTH)

AF:

0.538

AC:

14678

AN:

27278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

9744

19488

29233

38977

48721

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15886

31772

47658

63544

79430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.521

AC:

79234

AN:

152042

Hom.:

20822

Cov.:

AF XY:

0.522

AC XY:

38765

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.523

AC:

21688

AN:

41432

American (AMR)

AF:

0.438

AC:

6689

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.579

AC:

2009

AN:

3468

East Asian (EAS)

AF:

0.489

AC:

2535

AN:

5184

South Asian (SAS)

AF:

0.571

AC:

2751

AN:

4822

European-Finnish (FIN)

AF:

0.550

AC:

5820

AN:

10580

Middle Eastern (MID)

AF:

0.483

AC:

142

AN:

294

European-Non Finnish (NFE)

AF:

0.534

AC:

36272

AN:

67974

Other (OTH)

AF:

0.504

AC:

1063

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1949

3897

5846

7794

9743

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

702

1404

2106

2808

3510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.528

Hom.:

43880

Bravo

AF:

0.510

Asia WGS

AF:

0.535

AC:

1861

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

(source)

DANN

Benign

0.34

PhyloP100

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over