rs142403002

Variant names:

• chr10-17157650-A-C
• rs142403002
• NM_004412.7:c.678T>G

Your query was ambiguous. Multiple possible variants found:

• chr10-17157650-A-C
• chr10-17157650-A-G
• chr10-17157650-A-T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_004412.7(TRDMT1):​c.678T>G​(p.Asp226Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000572 in 1,613,644 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0032 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00029 (2 hom.)
• Consequence: TRDMT1 NM_004412.7 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.496
• Publications: 0 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0025156736).
• BP6: Variant 10-17157650-A-C is Benign according to our data. Variant chr10-17157650-A-C is described in ClinVar as Benign. ClinVar VariationId is 769768.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 3 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.678T>G	p.Asp226Glu	missense	Exon 8 of 11	NP_004403.1	O14717-1
	TRDMT1	NM_001351219.2		c.678T>G	p.Asp226Glu	missense	Exon 8 of 11	NP_001338148.1
	TRDMT1	NM_001351220.2		c.678T>G	p.Asp226Glu	missense	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.678T>G	p.Asp226Glu	missense	Exon 8 of 11	ENSP00000367030.3	O14717-1
	TRDMT1	ENST00000354631.7	TSL:1	n.*698T>G		non_coding_transcript_exon	Exon 9 of 12	ENSP00000346652.3	Q7Z3E4
	TRDMT1	ENST00000354631.7	TSL:1	n.*698T>G		3_prime_UTR	Exon 9 of 12	ENSP00000346652.3	Q7Z3E4

Frequencies

GnomAD3 genomes AF: 0.00323 AC: 492 AN: 152196 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0114

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.000724 AC: 181 AN: 250082 AF XY: 0.000540

Gnomad AFR exome AF: 0.0103

Gnomad AMR exome AF: 0.000261

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.000492

GnomAD4 exome AF: 0.000294 AC: 430 AN: 1461330 Hom.: 2 Cov.: 34 AF XY: 0.000259 AC XY: 188 AN XY: 726910

African (AFR) AF: 0.0110 AC: 367 AN: 33474

American (AMR) AF: 0.000313 AC: 14 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39652

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53310

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5762

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111758

Other (OTH) AF: 0.000712 AC: 43 AN: 60372

GnomAD4 genome AF: 0.00324 AC: 493 AN: 152314 Hom.: 3 Cov.: 33 AF XY: 0.00303 AC XY: 226 AN XY: 74478

African (AFR) AF: 0.0114 AC: 473 AN: 41578

American (AMR) AF: 0.000849 AC: 13 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68008

Other (OTH) AF: 0.00284 AC: 6 AN: 2112

Alfa AF: 0.00104 Hom.: 2

Bravo AF: 0.00396

ESP6500AA AF: 0.0102 AC: 45

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000931 AC: 113

EpiCase AF: 0.00

EpiControl AF: 0.0000595

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
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	1.4
DANN	Benign	0.96
DEOGEN2	Benign	0.35	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.68	T
MetaRNN	Benign	0.0025	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.54	N
PhyloP100		-0.50
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.070	N
REVEL	Benign	0.044
Sift	Benign	0.70	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.020
MutPred		0.44		Gain of methylation at K225 (P = 0.0901)
MVP		0.36
MPC		0.016
ClinPred		0.0024	T
GERP RS		0.086
Varity_R		0.033
gMVP		0.29
Mutation Taster		=93/7	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: rs142403002; hg19: chr10-17199649;