20-18593800-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_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

Scores

7
10
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.48
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
DTD1NM_080820.6 linkc.113C>T p.Thr38Met missense_variant Exon 2 of 6 ENST00000377452.4 NP_543010.3 Q8TEA8
DTD1NM_001318043.2 linkc.113C>T p.Thr38Met missense_variant Exon 2 of 5 NP_001304972.1 Q8TEA8A0A2R8Y6X2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DTD1ENST00000377452.4 linkc.113C>T p.Thr38Met missense_variant Exon 2 of 6 1 NM_080820.6 ENSP00000366672.4 Q8TEA8
ENSG00000284776ENST00000618693.4 linkc.188C>T p.Thr63Met missense_variant Exon 2 of 5 5 ENSP00000482916.1 A0A087WZV9
DTD1ENST00000494921.2 linkc.113C>T p.Thr38Met missense_variant Exon 2 of 5 2 ENSP00000495845.1 A0A2R8Y6X2
DTD1ENST00000647441.1 linkn.113C>T non_coding_transcript_exon_variant Exon 2 of 7 ENSP00000493969.1 A0A2R8YCT7

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
show subpopulations
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
show subpopulations
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
LINK: link

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs868148836; hg19: chr20-18574444; API