20-18593800-C-T

Variant names:

• chr20-18593800-C-T
• rs868148836
• NM_080820.6:c.113C>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_080820.6(DTD1):​c.113C>T​(p.Thr38Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,338 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: DTD1 NM_080820.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.48

Genes affected

DTD1 (HGNC:16219): (D-aminoacyl-tRNA deacylase 1) The protein encoded by this gene is similar in sequence to histidyl-tRNA synthetase, which hydrolyzes D-tyrosyl-tRNA(Tyr) into D-tyrosine and free tRNA(Tyr). The encoded protein binds the DNA unwinding element and plays a role in the initiation of DNA replication. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

ENSG00000284776 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.846

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTD1	NM_080820.6	c.113C>T	p.Thr38Met	missense_variant	Exon 2 of 6	ENST00000377452.4	NP_543010.3
DTD1	NM_001318043.2	c.113C>T	p.Thr38Met	missense_variant	Exon 2 of 5		NP_001304972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTD1	ENST00000377452.4	c.113C>T	p.Thr38Met	missense_variant	Exon 2 of 6	1	NM_080820.6	ENSP00000366672.4
ENSG00000284776	ENST00000618693.4	c.188C>T	p.Thr63Met	missense_variant	Exon 2 of 5	5		ENSP00000482916.1
DTD1	ENST00000494921.2	c.113C>T	p.Thr38Met	missense_variant	Exon 2 of 5	2		ENSP00000495845.1
DTD1	ENST00000647441.1	n.113C>T		non_coding_transcript_exon_variant	Exon 2 of 7			ENSP00000493969.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000797 AC: 2 AN: 251050 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135682

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461338 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726980

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000322 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 14, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.113C>T (p.T38M) alteration is located in exon 2 (coding exon 2) of the DTD1 gene. This alteration results from a C to T substitution at nucleotide position 113, causing the threonine (T) at amino acid position 38 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	26
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.50	.;D;.
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Uncertain	0.20	D
MetaRNN	Pathogenic	0.85	D;D;D
MetaSVM	Uncertain	0.15	D
MutationAssessor	Pathogenic	4.3	.;H;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-5.0	.;D;.
REVEL	Uncertain	0.45
Sift	Uncertain	0.0080	.;D;.
Sift4G	Uncertain	0.0020	D;D;.
Polyphen		0.59	.;P;.
Vest4		0.35
MutPred		0.65		.;Gain of catalytic residue at T38 (P = 0.0857);Gain of catalytic residue at T38 (P = 0.0857);
MVP		0.52
MPC		1.2
ClinPred		0.99	D
GERP RS		6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.32
gMVP		0.46

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: rs868148836; hg19: chr20-18574444;