20-18588109-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_080820.6(DTD1):c.37G>A(p.Val13Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 151,952 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 8.7e-7 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
DTD1
NM_080820.6 missense
NM_080820.6 missense
Scores
2
9
8
Clinical Significance
Conservation
PhyloP100: 4.98
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, 0.916
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DTD1 | NM_080820.6 | c.37G>A | p.Val13Ile | missense_variant | 1/6 | ENST00000377452.4 | |
DTD1 | NM_001318043.2 | c.37G>A | p.Val13Ile | missense_variant | 1/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DTD1 | ENST00000377452.4 | c.37G>A | p.Val13Ile | missense_variant | 1/6 | 1 | NM_080820.6 | P1 | |
DTD1 | ENST00000494921.2 | c.37G>A | p.Val13Ile | missense_variant | 1/5 | 2 | |||
DTD1 | ENST00000647441.1 | c.37G>A | p.Val13Ile | missense_variant, NMD_transcript_variant | 1/7 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151952Hom.: 0 Cov.: 32
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 8.65e-7 AC: 1AN: 1155820Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 557138
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
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GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151952Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74222
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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 | Aug 30, 2022 | The c.37G>A (p.V13I) alteration is located in exon 1 (coding exon 1) of the DTD1 gene. This alteration results from a G to A substitution at nucleotide position 37, causing the valine (V) at amino acid position 13 to be replaced by an isoleucine (I). 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
D
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Uncertain
D;.
Sift4G
Uncertain
D;.
Polyphen
P;.
Vest4
MutPred
Loss of catalytic residue at V13 (P = 0.1086);Loss of catalytic residue at V13 (P = 0.1086);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at