15-74655920-A-C
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_025083.5(EDC3):c.633T>G(p.Ala211=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000457 in 1,614,132 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00049 ( 1 hom., cov: 31)
Exomes 𝑓: 0.00045 ( 6 hom. )
Consequence
EDC3
NM_025083.5 synonymous
NM_025083.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.413
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 Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
?
Variant 15-74655920-A-C is Benign according to our data. Variant chr15-74655920-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 754638.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.413 with no splicing effect.
BS2
?
High Homozygotes in GnomAdExome at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EDC3 | NM_025083.5 | c.633T>G | p.Ala211= | synonymous_variant | 4/7 | ENST00000315127.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EDC3 | ENST00000315127.9 | c.633T>G | p.Ala211= | synonymous_variant | 4/7 | 1 | NM_025083.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000493 AC: 75AN: 152120Hom.: 1 Cov.: 31
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GnomAD3 exomes AF: 0.000768 AC: 193AN: 251464Hom.: 2 AF XY: 0.000809 AC XY: 110AN XY: 135906
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GnomAD4 exome AF: 0.000453 AC: 662AN: 1461894Hom.: 6 Cov.: 32 AF XY: 0.000463 AC XY: 337AN XY: 727248
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GnomAD4 genome ? AF: 0.000493 AC: 75AN: 152238Hom.: 1 Cov.: 31 AF XY: 0.000511 AC XY: 38AN XY: 74416
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
EDC3-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 16, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
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Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at