chr20-18628159-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_080820.6(DTD1):c.403A>G(p.Ile135Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000917 in 1,613,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000090 ( 0 hom. )
Consequence
DTD1
NM_080820.6 missense
NM_080820.6 missense
Scores
1
7
6
Clinical Significance
Conservation
PhyloP100: 7.63
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 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.32744813).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DTD1 | NM_080820.6 | c.403A>G | p.Ile135Val | missense_variant | 4/6 | ENST00000377452.4 | |
DTD1 | NM_001318043.2 | c.403A>G | p.Ile135Val | missense_variant | 4/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DTD1 | ENST00000377452.4 | c.403A>G | p.Ile135Val | missense_variant | 4/6 | 1 | NM_080820.6 | P1 | |
DTD1 | ENST00000494921.2 | c.403A>G | p.Ile135Val | missense_variant | 4/5 | 2 | |||
DTD1 | ENST00000647441.1 | c.*66A>G | 3_prime_UTR_variant, NMD_transcript_variant | 5/7 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152116Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000477 AC: 12AN: 251384Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135870
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GnomAD4 exome AF: 0.0000903 AC: 132AN: 1461688Hom.: 0 Cov.: 31 AF XY: 0.0000894 AC XY: 65AN XY: 727092
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GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152116Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74304
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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 | Jun 06, 2023 | The c.403A>G (p.I135V) alteration is located in exon 4 (coding exon 4) of the DTD1 gene. This alteration results from a A to G substitution at nucleotide position 403, causing the isoleucine (I) at amino acid position 135 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
Sift4G
Benign
T;T;.
Polyphen
0.87
.;P;.
Vest4
0.48
MVP
MPC
0.78
ClinPred
T
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