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GeneBe

15-74635417-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_025083.5(EDC3):c.1184G>A(p.Ser395Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

EDC3
NM_025083.5 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.64
Variant links:
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]
CLK3 (HGNC:2071): (CDC like kinase 3) This gene encodes a protein belonging to the serine/threonine type protein kinase family. This protein is a nuclear dual-specificity kinase that regulates the intranuclear distribution of the serine/arginine-rich (SR) family of splicing factors. Two transcript variants encoding different isoforms have been found for this gene. Related pseudogenes are located on chromosomes 1 and 9. [provided by RefSeq, Jul 2008]

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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=0.13862741).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EDC3NM_025083.5 linkuse as main transcriptc.1184G>A p.Ser395Asn missense_variant 6/7 ENST00000315127.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EDC3ENST00000315127.9 linkuse as main transcriptc.1184G>A p.Ser395Asn missense_variant 6/71 NM_025083.5 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

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 submitterclinical testingAmbry GeneticsJul 25, 2023The c.1184G>A (p.S395N) alteration is located in exon 9 (coding exon 5) of the EDC3 gene. This alteration results from a G to A substitution at nucleotide position 1184, causing the serine (S) at amino acid position 395 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.65
Cadd
Benign
21
Dann
Benign
0.90
DEOGEN2
Benign
0.027
T;T;T;T
Eigen
Benign
-0.29
Eigen_PC
Benign
-0.11
FATHMM_MKL
Uncertain
0.87
D
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.14
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.99
L;L;L;L
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-0.87
N;.;N;N
REVEL
Benign
0.058
Sift
Benign
0.52
T;.;T;T
Sift4G
Benign
0.26
T;.;T;T
Polyphen
0.0080
B;B;B;B
Vest4
0.16
MutPred
0.35
Loss of disorder (P = 0.0834);Loss of disorder (P = 0.0834);Loss of disorder (P = 0.0834);Loss of disorder (P = 0.0834);
MVP
0.48
MPC
0.46
ClinPred
0.45
T
GERP RS
4.1
Varity_R
0.34
gMVP
0.39

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-74927758; API