NM_004412.7:c.1091T>C

Variant names:

• chr10-17149125-A-G
• NM_004412.7:c.1091T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004412.7(TRDMT1):​c.1091T>C​(p.Ile364Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRDMT1 NM_004412.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.20
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24430415).

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.1091T>C	p.Ile364Thr	missense	Exon 11 of 11	NP_004403.1	O14717-1
	TRDMT1	NM_001351219.2		c.1070T>C	p.Ile357Thr	missense	Exon 11 of 11	NP_001338148.1
	TRDMT1	NM_001351221.2		c.932T>C	p.Ile311Thr	missense	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.1091T>C	p.Ile364Thr	missense	Exon 11 of 11	ENSP00000367030.3	O14717-1
	TRDMT1	ENST00000354631.7	TSL:1	n.*1111T>C		non_coding_transcript_exon	Exon 12 of 12	ENSP00000346652.3	Q7Z3E4
	TRDMT1	ENST00000354631.7	TSL:1	n.*1111T>C		3_prime_UTR	Exon 12 of 12	ENSP00000346652.3	Q7Z3E4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	20
DANN	Benign	0.78
DEOGEN2	Uncertain	0.65	D
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.3	L
PhyloP100		5.2
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.23
Sift	Benign	0.66	T
Sift4G	Benign	0.56	T
Polyphen		0.0040	B
Vest4		0.069
MutPred		0.61		Gain of disorder (P = 0.0087)
MVP		0.75
MPC		0.023
ClinPred		0.37	T
GERP RS		3.2
Varity_R		0.15
gMVP		0.46
Mutation Taster		=67/33	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

hg19: chr10-17191124;