chr20-18593777-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_080820.6(DTD1):c.90G>T(p.Leu30Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000143 in 1,613,914 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: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000068 ( 0 hom. )
Consequence
DTD1
NM_080820.6 missense
NM_080820.6 missense
Scores
3
6
5
Clinical Significance
Conservation
PhyloP100: 3.62
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 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.808
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DTD1 | NM_080820.6 | c.90G>T | p.Leu30Phe | missense_variant | 2/6 | ENST00000377452.4 | |
DTD1 | NM_001318043.2 | c.90G>T | p.Leu30Phe | missense_variant | 2/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DTD1 | ENST00000377452.4 | c.90G>T | p.Leu30Phe | missense_variant | 2/6 | 1 | NM_080820.6 | P1 | |
DTD1 | ENST00000494921.2 | c.90G>T | p.Leu30Phe | missense_variant | 2/5 | 2 | |||
DTD1 | ENST00000647441.1 | c.90G>T | p.Leu30Phe | missense_variant, NMD_transcript_variant | 2/7 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152184Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251292Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135804
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GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461730Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 727182
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GnomAD4 genome ? AF: 0.0000854 AC: 13AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74336
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 08, 2024 | The c.90G>T (p.L30F) alteration is located in exon 2 (coding exon 2) of the DTD1 gene. This alteration results from a G to T substitution at nucleotide position 90, causing the leucine (L) at amino acid position 30 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Pathogenic
T
Sift4G
Benign
T;T;.
Polyphen
1.0
.;D;.
Vest4
0.79
MutPred
0.82
.;Loss of catalytic residue at L30 (P = 0.061);Loss of catalytic residue at L30 (P = 0.061);
MVP
MPC
1.2
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at