Genetic Variant NM_005711.5:c.782A>G (chr5-84066476-T-C) – 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_005711.5(EDIL3):c.782A>G(p.Lys261Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000412 in 1,456,354 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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: 0.0000041 ( 0 hom. )

Consequence

EDIL3
NM_005711.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.58

Publications

0 publications found

Variant links:

Genes affected

EDIL3 (HGNC:3173): (EGF like repeats and discoidin domains 3) The protein encoded by this gene is an integrin ligand. It plays an important role in mediating angiogenesis and may be important in vessel wall remodeling and development. It also influences endothelial cell behavior. [provided by RefSeq, Jul 2008]

EDIL3 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=0.30083033).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDIL3	NM_005711.5 link	c.782A>G	p.Lys261Arg	missense_variant	Exon 7 of 11	ENST00000296591.10	NP_005702.3	O43854-1
EDIL3	NM_001278642.1 link	c.752A>G	p.Lys251Arg	missense_variant	Exon 6 of 10		NP_001265571.1	O43854-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EDIL3	ENST00000296591.10 link	c.782A>G	p.Lys261Arg	missense_variant	Exon 7 of 11	1	NM_005711.5	ENSP00000296591.4	O43854-1
EDIL3	ENST00000380138.3 link	c.752A>G	p.Lys251Arg	missense_variant	Exon 6 of 10	1		ENSP00000369483.3	O43854-2
EDIL3	ENST00000510271.1 link	n.331A>G		non_coding_transcript_exon_variant	Exon 2 of 5	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000412

AC:

AN:

1456354

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

724206

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33132

American (AMR)

AF:

0.00

AC:

AN:

43304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26042

East Asian (EAS)

AF:

0.00

AC:

AN:

39418

South Asian (SAS)

AF:

0.00

AC:

AN:

84476

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00000540

AC:

AN:

1110654

Other (OTH)

AF:

0.00

AC:

AN:

60194

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 04, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.782A>G (p.K261R) alteration is located in exon 7 (coding exon 7) of the EDIL3 gene. This alteration results from a A to G substitution at nucleotide position 782, causing the lysine (K) at amino acid position 261 to be replaced by an arginine (R). 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

0.076

BayesDel_addAF

Uncertain

0.096

BayesDel_noAF

Benign

-0.10

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.54

D;.

Eigen

Benign

-0.0098

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.85

T;T

M_CAP

Benign

0.070

MetaRNN

Benign

0.30

T;T

MetaSVM

Pathogenic

0.81

MutationAssessor

Benign

0.35

N;.

PhyloP100

2.6

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.78

N;N

REVEL

Uncertain

0.49

Sift

Benign

0.41

T;T

Sift4G

Benign

0.60

T;T

Polyphen

0.33

B;D

Vest4

0.17

MutPred

0.57

Loss of methylation at K261 (P = 0.0201);.;

MVP

0.93

MPC

0.21

ClinPred

0.70

GERP RS

4.9

Varity_R

0.19

gMVP

0.59

Mutation Taster

=92/8

polymorphism

(source)

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

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NM_005711.5:c.782A>G

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