Genetic Variant TRDMT1:n.*3761G>A (chr10-17146475-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000354631.7(TRDMT1):n.*3761G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.986 in 985,376 control chromosomes in the GnomAD database, including 480,023 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 0.95 ( 68783 hom., cov: 33)

Exomes 𝑓: 0.99 ( 411240 hom. )

Consequence

TRDMT1
ENST00000354631.7 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.05

Publications

8 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=-0.96).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRDMT1	NM_004412.7 link	c.*2565G>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000377799.8	NP_004403.1	O14717-1Q6ICS7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRDMT1	ENST00000354631.7 link	n.*3761G>A	non_coding_transcript_exon_variant	Exon 12 of 12	1		ENSP00000346652.3	Q7Z3E4
TRDMT1	ENST00000377799.8 link	c.*2565G>A	3_prime_UTR_variant	Exon 11 of 11	1	NM_004412.7	ENSP00000367030.3	O14717-1
TRDMT1	ENST00000354631.7 link	n.*3761G>A	3_prime_UTR_variant	Exon 12 of 12	1		ENSP00000346652.3	Q7Z3E4

Frequencies

GnomAD3 genomes

AF:

0.948

AC:

144275

AN:

152168

Hom.:

68762

Cov.:

show subpopulations

Gnomad AFR

AF:

0.924

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.840

Gnomad ASJ

AF:

0.993

Gnomad EAS

AF:

0.734

Gnomad SAS

AF:

0.928

Gnomad FIN

AF:

0.971

Gnomad MID

AF:

0.994

Gnomad NFE

AF:

0.998

Gnomad OTH

AF:

0.963

GnomAD4 exome

AF:

0.993

AC:

827501

AN:

833090

Hom.:

411240

Cov.:

AF XY:

0.994

AC XY:

382203

AN XY:

384700

show subpopulations

African (AFR)

AF:

0.916

AC:

14454

AN:

15778

American (AMR)

AF:

0.799

AC:

786

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.994

AC:

5119

AN:

5152

East Asian (EAS)

AF:

0.755

AC:

2739

AN:

3630

South Asian (SAS)

AF:

0.937

AC:

15418

AN:

16458

European-Finnish (FIN)

AF:

0.971

AC:

268

AN:

276

Middle Eastern (MID)

AF:

0.989

AC:

1602

AN:

1620

European-Non Finnish (NFE)

AF:

0.998

AC:

760548

AN:

761896

Other (OTH)

AF:

0.973

AC:

26567

AN:

27296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.427

Heterozygous variant carriers

318

637

955

1274

1592

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20278

40556

60834

81112

101390

<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:

0.948

AC:

144341

AN:

152286

Hom.:

68783

Cov.:

AF XY:

0.941

AC XY:

70103

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.923

AC:

38353

AN:

41548

American (AMR)

AF:

0.839

AC:

12820

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.993

AC:

3447

AN:

3472

East Asian (EAS)

AF:

0.733

AC:

3787

AN:

5164

South Asian (SAS)

AF:

0.929

AC:

4485

AN:

4830

European-Finnish (FIN)

AF:

0.971

AC:

10320

AN:

10628

Middle Eastern (MID)

AF:

0.993

AC:

292

AN:

294

European-Non Finnish (NFE)

AF:

0.998

AC:

67894

AN:

68044

Other (OTH)

AF:

0.964

AC:

2033

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

342

685

1027

1370

1712

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

908

1816

2724

3632

4540

<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:

0.976

Hom.:

215220

Bravo

AF:

0.935

Asia WGS

AF:

0.877

AC:

3052

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.43

(source)

DANN

Benign

0.42

PhyloP100

-1.0

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over