rs868148836

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_080820.6(DTD1):​c.113C>A​(p.Thr38Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,338 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T38M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DTD1
NM_080820.6 missense

Scores

4
9
6

Clinical Significance

Not reported in ClinVar

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]

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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, 0.84

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DTD1NM_080820.6 linkc.113C>A p.Thr38Lys missense_variant Exon 2 of 6 ENST00000377452.4 NP_543010.3 Q8TEA8
DTD1NM_001318043.2 linkc.113C>A p.Thr38Lys 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>A p.Thr38Lys missense_variant Exon 2 of 6 1 NM_080820.6 ENSP00000366672.4 Q8TEA8
ENSG00000284776ENST00000618693.4 linkc.188C>A p.Thr63Lys missense_variant Exon 2 of 5 5 ENSP00000482916.1 A0A087WZV9
DTD1ENST00000494921.2 linkc.113C>A p.Thr38Lys missense_variant Exon 2 of 5 2 ENSP00000495845.1 A0A2R8Y6X2
DTD1ENST00000647441.1 linkn.113C>A non_coding_transcript_exon_variant Exon 2 of 7 ENSP00000493969.1 A0A2R8YCT7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461338
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
726980
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.27
BayesDel_addAF
Pathogenic
0.23
D
BayesDel_noAF
Uncertain
0.090
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.38
.;T;.
Eigen
Uncertain
0.45
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.88
D;D;D
M_CAP
Benign
0.015
T
MetaRNN
Pathogenic
0.84
D;D;D
MetaSVM
Benign
-0.43
T
MutationAssessor
Uncertain
2.8
.;M;.
PrimateAI
Uncertain
0.69
T
PROVEAN
Pathogenic
-4.6
.;D;.
REVEL
Uncertain
0.55
Sift
Uncertain
0.022
.;D;.
Sift4G
Benign
0.072
T;D;.
Polyphen
0.21
.;B;.
Vest4
0.54
MutPred
0.69
.;Gain of ubiquitination at T38 (P = 0.0162);Gain of ubiquitination at T38 (P = 0.0162);
MVP
0.41
MPC
0.57
ClinPred
0.98
D
GERP RS
6.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.56
gMVP
0.61

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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