NM_004412.7:c.547C>T

Variant names:

• chr10-17157781-G-A
• rs115493360
• NM_004412.7:c.547C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_004412.7(TRDMT1):​c.547C>T​(p.Leu183Leu) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.531
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.026).
• BP6: Variant 10-17157781-G-A is Benign according to our data. Variant chr10-17157781-G-A is described in ClinVar as Benign. ClinVar VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 19 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004412.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRDMT1	NM_004412.7	MANE Select	c.547C>T	p.Leu183Leu	synonymous	Exon 8 of 11	NP_004403.1	O14717-1
	TRDMT1	NM_001351219.2		c.547C>T	p.Leu183Leu	synonymous	Exon 8 of 11	NP_001338148.1
	TRDMT1	NM_001351220.2		c.547C>T	p.Leu183Leu	synonymous	Exon 8 of 11	NP_001338149.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRDMT1	ENST00000377799.8	TSL:1 MANE Select	c.547C>T	p.Leu183Leu	synonymous	Exon 8 of 11	ENSP00000367030.3	O14717-1
	TRDMT1	ENST00000354631.7	TSL:1	n.*567C>T		non_coding_transcript_exon	Exon 9 of 12	ENSP00000346652.3	Q7Z3E4
	TRDMT1	ENST00000354631.7	TSL:1	n.*567C>T		3_prime_UTR	Exon 9 of 12	ENSP00000346652.3	Q7Z3E4

Frequencies

GnomAD3 genomes AF: 0.00926 AC: 1409 AN: 152108 Hom.: 19 Cov.: 33

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

GnomAD2 exomes AF: 0.00274 AC: 591 AN: 215742 AF XY: 0.00184

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 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.: 19 Cov.: 30 AF XY: 0.000846 AC XY: 589 AN XY: 696026

African (AFR) AF: 0.0364 AC: 1135 AN: 31216

American (AMR) AF: 0.00158 AC: 56 AN: 35516

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23968

East Asian (EAS) AF: 0.00 AC: 0 AN: 39114

South Asian (SAS) AF: 0.0000632 AC: 5 AN: 79100

European-Finnish (FIN) AF: 0.0000208 AC: 1 AN: 48100

Middle Eastern (MID) AF: 0.00248 AC: 10 AN: 4026

European-Non Finnish (NFE) AF: 0.0000478 AC: 52 AN: 1088114

Other (OTH) AF: 0.00186 AC: 108 AN: 57978

GnomAD4 genome AF: 0.00927 AC: 1411 AN: 152226 Hom.: 19 Cov.: 33 AF XY: 0.00887 AC XY: 660 AN XY: 74426

African (AFR) AF: 0.0326 AC: 1352 AN: 41528

American (AMR) AF: 0.00170 AC: 26 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68012

Other (OTH) AF: 0.00758 AC: 16 AN: 2110

Alfa AF: 0.00428 Hom.: 2

Bravo AF: 0.0106

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.1
DANN	Benign	0.65
PhyloP100		0.53
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs115493360; hg19: chr10-17199780;