chr15-74656039-C-G
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_025083.5(EDC3):āc.514G>Cā(p.Ala172Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000256 in 1,612,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00011 ( 0 hom., cov: 31)
Exomes š: 0.00027 ( 0 hom. )
Consequence
EDC3
NM_025083.5 missense
NM_025083.5 missense
Scores
3
15
Clinical Significance
Conservation
PhyloP100: 3.61
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 1 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=0.1466816).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EDC3 | NM_025083.5 | c.514G>C | p.Ala172Pro | missense_variant | 4/7 | ENST00000315127.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EDC3 | ENST00000315127.9 | c.514G>C | p.Ala172Pro | missense_variant | 4/7 | 1 | NM_025083.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 151412Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000996 AC: 25AN: 251106Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135804
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GnomAD4 exome AF: 0.000270 AC: 395AN: 1460700Hom.: 0 Cov.: 31 AF XY: 0.000246 AC XY: 179AN XY: 726492
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GnomAD4 genome AF: 0.000112 AC: 17AN: 151412Hom.: 0 Cov.: 31 AF XY: 0.000122 AC XY: 9AN XY: 73848
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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 | Mar 29, 2022 | The c.514G>C (p.A172P) alteration is located in exon 7 (coding exon 3) of the EDC3 gene. This alteration results from a G to C substitution at nucleotide position 514, causing the alanine (A) at amino acid position 172 to be replaced by a proline (P). 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
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;L;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N;N;N;N
REVEL
Benign
Sift
Benign
T;.;T;T;D;D
Sift4G
Benign
T;.;T;T;T;.
Polyphen
B;B;B;B;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
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