dbSNP rs766126304: EDC4:p.Glu32Gly (chr16-67875957-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_014329.5(EDC4):c.95A>G(p.Glu32Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,270 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

EDC4
NM_014329.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.39

Publications

0 publications found

Variant links:

Genes affected

EDC4 (HGNC:17157): (enhancer of mRNA decapping 4) Predicted to be involved in deadenylation-independent decapping of nuclear-transcribed mRNA. Located in P-body and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

EDC4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3122863).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDC4	NM_014329.5 link	c.95A>G	p.Glu32Gly	missense_variant	Exon 2 of 29	ENST00000358933.10	NP_055144.3	Q6P2E9-1
EDC4	NM_001427345.1 link	c.95A>G	p.Glu32Gly	missense_variant	Exon 2 of 28		NP_001414274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EDC4	ENST00000358933.10 link	c.95A>G	p.Glu32Gly	missense_variant	Exon 2 of 29	1	NM_014329.5	ENSP00000351811.5	Q6P2E9-1
EDC4	ENST00000536072.6 link	n.100A>G		non_coding_transcript_exon_variant	Exon 2 of 17	2
EDC4	ENST00000572221.5 link	n.405A>G		non_coding_transcript_exon_variant	Exon 3 of 28	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000120

AC:

AN:

250964

AF XY:

0.00000737

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461270

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726948

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

33468

American (AMR)

AF:

0.0000224

AC:

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53366

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5558

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111778

Other (OTH)

AF:

0.00

AC:

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 15, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.95A>G (p.E32G) alteration is located in exon 2 (coding exon 2) of the EDC4 gene. This alteration results from a A to G substitution at nucleotide position 95, causing the glutamic acid (E) at amino acid position 32 to be replaced by a glycine (G). 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

0.12

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.70

M_CAP

Benign

0.0021

MetaRNN

Benign

0.31

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.9

PhyloP100

6.4

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.2

REVEL

Benign

0.045

Sift

Uncertain

0.016

Sift4G

Uncertain

0.018

Polyphen

0.28

Vest4

0.58

MutPred

0.30

Loss of sheet (P = 0.0011);

MVP

0.23

MPC

1.1

ClinPred

0.36

GERP RS

5.9

Varity_R

0.090

gMVP

0.32

Mutation Taster

=72/28

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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rs766126304

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over