rs370715356

Variant names:

• chr10-17159229-G-C
• rs370715356
• NM_004412.7:c.460C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-17159229-G-C
• chr10-17159229-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004412.7(TRDMT1):​c.460C>G​(p.Leu154Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: TRDMT1 NM_004412.7 missense, splice_region
• Scores: Splicing: ADA: 0.0006367
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.07

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3935516).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRDMT1	NM_004412.7	c.460C>G	p.Leu154Val	missense_variant, splice_region_variant	Exon 7 of 11	ENST00000377799.8	NP_004403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRDMT1	ENST00000377799.8	c.460C>G	p.Leu154Val	missense_variant, splice_region_variant	Exon 7 of 11	1	NM_004412.7	ENSP00000367030.3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152104 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152104 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74302

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000192

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Uncertain	0.57	D;.
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.96	N;N
REVEL	Benign	0.049
Sift	Benign	0.17	T;T
Sift4G	Benign	0.068	T;.
Polyphen		0.0	B;.
Vest4		0.31
MutPred		0.60		Loss of loop (P = 0.2237);.;
MVP		0.57
MPC		0.016
ClinPred		0.39	T
GERP RS		3.8
Varity_R		0.25
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00064
dbscSNV1_RF	Benign	0.13
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: rs370715356; hg19: chr10-17201228;