10-17146642-T-C

Position:

• chr10-17146642-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRDMT1	NM_004412.7	c.*2398A>G		3_prime_UTR_variant	11/11	ENST00000377799.8	NP_004403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRDMT1	ENST00000377799.8	c.*2398A>G		3_prime_UTR_variant	11/11	1	NM_004412.7	ENSP00000367030.3
TRDMT1	ENST00000354631.7	n.*3594A>G		non_coding_transcript_exon_variant	12/12	1		ENSP00000346652.3
TRDMT1	ENST00000354631.7	n.*3594A>G		3_prime_UTR_variant	12/12	1		ENSP00000346652.3

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

Gnomad4 AFR exome AF: 0.131

Gnomad4 AMR exome AF: 0.390

Gnomad4 ASJ exome AF: 0.615

Gnomad4 EAS exome AF: 0.523

Gnomad4 SAS exome AF: 0.568

Gnomad4 FIN exome AF: 0.529

Gnomad4 NFE exome AF: 0.531

Gnomad4 OTH exome AF: 0.517

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

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.394

Gnomad4 ASJ AF: 0.578

Gnomad4 EAS AF: 0.510

Gnomad4 SAS AF: 0.556

Gnomad4 FIN AF: 0.545

Gnomad4 NFE AF: 0.530

Gnomad4 OTH AF: 0.431

Alfa AF: 0.461 Hom.: 3945

Bravo AF: 0.391

Asia WGS AF: 0.516 AC: 1794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	10
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10904887; hg19: chr10-17188641;