15-74655775-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_025083.5(EDC3):c.778C>T(p.Arg260Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,764 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: not found (cov: 31)
Exomes 𝑓: 0.0000082 ( 0 hom. )
Consequence
EDC3
NM_025083.5 missense
NM_025083.5 missense
Scores
6
12
Clinical Significance
Conservation
PhyloP100: 1.73
Genes affected
EDC3 (HGNC:26114): (enhancer of mRNA decapping 3) This gene encodes a protein that is important in mRNA degradation. The encoded protein is a component of a decapping complex that promotes efficient removal of the monomethylguanosine (m7G) cap from mRNAs, as part of the 5' to 3' mRNA decay pathway. Mutations in this gene have been identified in human patients with an autosomal recessive form of intellectual disability. [provided by RefSeq, May 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, EDC3
BP4
Computational evidence support a benign effect (MetaRNN=0.33605945).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EDC3 | NM_025083.5 | c.778C>T | p.Arg260Trp | missense_variant | 4/7 | ENST00000315127.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EDC3 | ENST00000315127.9 | c.778C>T | p.Arg260Trp | missense_variant | 4/7 | 1 | NM_025083.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251380Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135872
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GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461764Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727162
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GnomAD4 genome Cov.: 31
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31
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Intellectual disability, autosomal recessive 50 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Breda Genetics srl | Jan 22, 2021 | Based on allele frequency, in-silico prediction scores and a certain overlap with the clinical phenotype, we interpreted this variant at least as of uncertain significance. The lack of one or more of the following features has discouraged further investigations: lack of a possible second hit in autosomal recessive conditions, presence of healthy controls in databases for autosomal dominant conditions, presence of unmatching cardinal clinical features in the patient or in the known gene-disease association, and/or variant type outside the known gene mutational spectrum. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;L;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;D;D;D
REVEL
Benign
Sift
Uncertain
D;.;D;D;D
Sift4G
Uncertain
D;.;D;D;.
Polyphen
D;D;D;D;.
Vest4
MutPred
Loss of disorder (P = 0.0281);Loss of disorder (P = 0.0281);Loss of disorder (P = 0.0281);Loss of disorder (P = 0.0281);.;
MVP
MPC
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