20-18596191-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_080820.6(DTD1):c.320A>G(p.Asn107Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000452 in 1,614,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000045 ( 0 hom. )
Consequence
DTD1
NM_080820.6 missense
NM_080820.6 missense
Scores
2
12
Clinical Significance
Conservation
PhyloP100: 5.34
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 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.16252694).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DTD1 | NM_080820.6 | c.320A>G | p.Asn107Ser | missense_variant | 3/6 | ENST00000377452.4 | |
DTD1 | NM_001318043.2 | c.320A>G | p.Asn107Ser | missense_variant | 3/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DTD1 | ENST00000377452.4 | c.320A>G | p.Asn107Ser | missense_variant | 3/6 | 1 | NM_080820.6 | P1 | |
DTD1 | ENST00000494921.2 | c.320A>G | p.Asn107Ser | missense_variant | 3/5 | 2 | |||
DTD1 | ENST00000647441.1 | c.320A>G | p.Asn107Ser | missense_variant, NMD_transcript_variant | 3/7 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152134Hom.: 0 Cov.: 32
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?
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GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251382Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135864
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GnomAD4 exome AF: 0.0000451 AC: 66AN: 1461868Hom.: 0 Cov.: 32 AF XY: 0.0000399 AC XY: 29AN XY: 727238
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152134Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74314
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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 11, 2022 | The c.320A>G (p.N107S) alteration is located in exon 3 (coding exon 3) of the DTD1 gene. This alteration results from a A to G substitution at nucleotide position 320, causing the asparagine (N) at amino acid position 107 to be replaced by a serine (S). 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
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
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
Benign
T
Sift4G
Benign
T;T;.
Polyphen
0.0010
.;B;.
Vest4
0.16
MVP
MPC
0.32
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