rs3780962

Positions:

• chr10-17151347-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004412.7(TRDMT1):​c.1075+2160T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 984,470 control chromosomes in the GnomAD database, including 139,652 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 0.52 (20822 hom., cov: 32)
  • Exomes 𝑓: 0.53 (118830 hom.)
• Consequence: TRDMT1 NM_004412.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10

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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRDMT1	NM_004412.7	c.1075+2160T>C		intron_variant		ENST00000377799.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRDMT1	ENST00000377799.8	c.1075+2160T>C		intron_variant		1	NM_004412.7	P1
TRDMT1	ENST00000354631.7	c.*1095+2160T>C		intron_variant, NMD_transcript_variant		1
TRDMT1	ENST00000495022.5	c.*740+2160T>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79184 AN: 151924 Hom.: 20803 Cov.: 32

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.507

GnomAD4 exome AF: 0.534 AC: 444812 AN: 832428 Hom.: 118830 Cov.: 30 AF XY: 0.535 AC XY: 205671 AN XY: 384410

Gnomad4 AFR exome AF: 0.519

Gnomad4 AMR exome AF: 0.409

Gnomad4 ASJ exome AF: 0.615

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.584

Gnomad4 FIN exome AF: 0.533

Gnomad4 NFE exome AF: 0.533

Gnomad4 OTH exome AF: 0.538

GnomAD4 genome AF: 0.521 AC: 79234 AN: 152042 Hom.: 20822 Cov.: 32 AF XY: 0.522 AC XY: 38765 AN XY: 74328

Gnomad4 AFR AF: 0.523

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.489

Gnomad4 SAS AF: 0.571

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.504

Alfa AF: 0.534 Hom.: 11684

Bravo AF: 0.510

Asia WGS AF: 0.535 AC: 1861 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	11
DANN	Benign	0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs3780962; hg19: chr10-17193346;