NM_004412.7:c.*2398A>G

Variant names:

• chr10-17146642-T-C
• rs10904887
• NM_004412.7:c.*2398A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004412.7(TRDMT1):​c.*2398A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 983,652 control chromosomes in the GnomAD database, including 130,723 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 0.42 (15109 hom., cov: 32)
  • Exomes 𝑓: 0.52 (115614 hom.)
• Consequence: TRDMT1 NM_004412.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

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.*2398A>G		3_prime_UTR	Exon 11 of 11	NP_004403.1	O14717-1
	TRDMT1	NM_001351219.2		c.*2398A>G		3_prime_UTR	Exon 11 of 11	NP_001338148.1
	TRDMT1	NM_001351221.2		c.*2398A>G		3_prime_UTR	Exon 9 of 9	NP_001338150.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRDMT1	ENST00000377799.8	TSL:1 MANE Select	c.*2398A>G		3_prime_UTR	Exon 11 of 11	ENSP00000367030.3	O14717-1
	TRDMT1	ENST00000354631.7	TSL:1	n.*3594A>G		non_coding_transcript_exon	Exon 12 of 12	ENSP00000346652.3	Q7Z3E4
	TRDMT1	ENST00000354631.7	TSL:1	n.*3594A>G		3_prime_UTR	Exon 12 of 12	ENSP00000346652.3	Q7Z3E4

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63172 AN: 151668 Hom.: 15110 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.434

GnomAD4 exome AF: 0.524 AC: 436004 AN: 831866 Hom.: 115614 Cov.: 36 AF XY: 0.525 AC XY: 201800 AN XY: 384176

African (AFR) AF: 0.131 AC: 2074 AN: 15784

American (AMR) AF: 0.390 AC: 384 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 3163 AN: 5146

East Asian (EAS) AF: 0.523 AC: 1896 AN: 3622

South Asian (SAS) AF: 0.568 AC: 9339 AN: 16436

European-Finnish (FIN) AF: 0.529 AC: 146 AN: 276

Middle Eastern (MID) AF: 0.544 AC: 880 AN: 1618

European-Non Finnish (NFE) AF: 0.531 AC: 404030 AN: 760734

Other (OTH) AF: 0.517 AC: 14092 AN: 27266

GnomAD4 genome AF: 0.416 AC: 63169 AN: 151786 Hom.: 15109 Cov.: 32 AF XY: 0.419 AC XY: 31059 AN XY: 74142

African (AFR) AF: 0.167 AC: 6918 AN: 41486

American (AMR) AF: 0.394 AC: 6006 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 2003 AN: 3464

East Asian (EAS) AF: 0.510 AC: 2614 AN: 5122

South Asian (SAS) AF: 0.556 AC: 2682 AN: 4820

European-Finnish (FIN) AF: 0.545 AC: 5733 AN: 10516

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.530 AC: 35915 AN: 67822

Other (OTH) AF: 0.431 AC: 908 AN: 2106

Alfa AF: 0.462 Hom.: 6942

Bravo AF: 0.391

Asia WGS AF: 0.516 AC: 1794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	10
DANN	Benign	0.66
PhyloP100		-0.010
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10904887; hg19: chr10-17188641;