10-17160310-T-G

Variant names:

• chr10-17160310-T-G
• rs376428407
• NM_004412.7:c.454A>C

Variant summary

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

The NM_004412.7(TRDMT1):​c.454A>C​(p.Thr152Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000355 in 1,407,054 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: TRDMT1 NM_004412.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12

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=0.3052842).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRDMT1	NM_004412.7	c.454A>C	p.Thr152Pro	missense_variant	Exon 6 of 11	ENST00000377799.8	NP_004403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRDMT1	ENST00000377799.8	c.454A>C	p.Thr152Pro	missense_variant	Exon 6 of 11	1	NM_004412.7	ENSP00000367030.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000184 AC: 4 AN: 217054 Hom.: 0 AF XY: 0.0000255 AC XY: 3 AN XY: 117792

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000140

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000355 AC: 5 AN: 1407054 Hom.: 0 Cov.: 28 AF XY: 0.00000573 AC XY: 4 AN XY: 698686

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000105

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.21e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Pathogenic	0.81	D;.
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.081
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.076	D
MetaRNN	Benign	0.31	T;T
MetaSVM	Benign	-0.40	T
MutationAssessor	Uncertain	2.6	M;.
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Uncertain	0.51
Sift	Benign	0.040	D;T
Sift4G	Benign	0.17	T;.
Polyphen		0.0030	B;.
Vest4		0.33
MutPred		0.55		Gain of glycosylation at T152 (P = 0.0469);.;
MVP		0.91
MPC		0.017
ClinPred		0.20	T
GERP RS		2.0
Varity_R		0.77
gMVP		0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs376428407; hg19: chr10-17202309;