rs12780845

Variant names:

• chr10-17181245-A-G
• rs12780845
• NM_004412.7:c.65-6585T>C

Variant summary

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

The NM_004412.7(TRDMT1):​c.65-6585T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 151,932 control chromosomes in the GnomAD database, including 9,044 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 0.33 (9044 hom., cov: 31)
• Consequence: TRDMT1 NM_004412.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39
• Publications: 31 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRDMT1	NM_004412.7	c.65-6585T>C		intron_variant	Intron 1 of 10	ENST00000377799.8	NP_004403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRDMT1	ENST00000377799.8	c.65-6585T>C		intron_variant	Intron 1 of 10	1	NM_004412.7	ENSP00000367030.3

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50848 AN: 151812 Hom.: 9036 Cov.: 31

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.332

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.335 AC: 50885 AN: 151932 Hom.: 9044 Cov.: 31 AF XY: 0.328 AC XY: 24329 AN XY: 74262

African (AFR) AF: 0.442 AC: 18277 AN: 41388

American (AMR) AF: 0.251 AC: 3840 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 1152 AN: 3466

East Asian (EAS) AF: 0.207 AC: 1070 AN: 5166

South Asian (SAS) AF: 0.252 AC: 1211 AN: 4812

European-Finnish (FIN) AF: 0.245 AC: 2582 AN: 10544

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.315 AC: 21430 AN: 67944

Other (OTH) AF: 0.337 AC: 712 AN: 2112

Alfa AF: 0.325 Hom.: 12386

Bravo AF: 0.342

Asia WGS AF: 0.256 AC: 889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.4
DANN	Benign	0.54
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs12780845; hg19: chr10-17223244;