11-126331461-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_014026.6(DCPS):c.433C>T(p.Arg145Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000384 in 1,614,152 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 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000040 ( 0 hom. )
Consequence
DCPS
NM_014026.6 missense
NM_014026.6 missense
Scores
5
14
Clinical Significance
Conservation
PhyloP100: 4.51
Genes affected
DCPS (HGNC:29812): (decapping enzyme, scavenger) This gene encodes a member of the histidine triad family of pyrophosphatases that removes short mRNA fragments containing the 5′ mRNA cap structure, which appear in the 3′ → 5′ mRNA decay pathway, following deadenylation and exosome-mediated turnover. This enzyme hydrolyzes the triphosphate linkage of the cap structure (7-methylguanosine nucleoside triphosphate) to yield 7-methylguanosine monophosphate and nucleoside diphosphate. It protects the cell from the potentially toxic accumulation of these short, capped mRNA fragments, and regulates the activity of other cap-binding proteins, which are inhibited by their accumulation. It also acts as a transcript-specific modulator of pre-mRNA splicing and microRNA turnover. [provided by RefSeq, Apr 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM1
?
In a mutagenesis_site Increases decapping activity to 180% of wild-type. (size 0) in uniprot entity DCPS_HUMAN
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.14717022).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DCPS | NM_014026.6 | c.433C>T | p.Arg145Cys | missense_variant | 3/6 | ENST00000263579.5 | |
DCPS | NM_001350236.2 | c.454C>T | p.Arg152Cys | missense_variant | 3/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DCPS | ENST00000263579.5 | c.433C>T | p.Arg145Cys | missense_variant | 3/6 | 1 | NM_014026.6 | P1 | |
DCPS | ENST00000648516.1 | c.154C>T | p.Arg52Cys | missense_variant | 4/7 | ||||
DCPS | ENST00000530860.5 | n.58C>T | non_coding_transcript_exon_variant | 1/3 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152152Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000915 AC: 23AN: 251480Hom.: 0 AF XY: 0.0000956 AC XY: 13AN XY: 135916
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GnomAD4 exome AF: 0.0000404 AC: 59AN: 1461882Hom.: 0 Cov.: 34 AF XY: 0.0000578 AC XY: 42AN XY: 727246
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 17, 2023 | The c.433C>T (p.R145C) alteration is located in exon 3 (coding exon 3) of the DCPS gene. This alteration results from a C to T substitution at nucleotide position 433, causing the arginine (R) at amino acid position 145 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 28, 2017 | The R145C variant in the DCPS gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R145C variant is observed in 4/8652 (0.05%) alleles from individuals of East Asian background in the ExAC dataset, and no individuals were reported to be homozygous (Lek et al., 2016). The R145C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, we interpret R145C as a variant of uncertain significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;.
REVEL
Benign
Sift
Benign
T;.
Sift4G
Benign
T;.
Polyphen
B;.
Vest4
MutPred
Loss of MoRF binding (P = 0.0053);.;
MVP
MPC
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