Variant 5-83943520-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005711.5(EDIL3):c.1342G>A(p.Asp448Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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

EDIL3
NM_005711.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.08

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:

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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;

BP4

Computational evidence support a benign effect (MetaRNN=0.2656695).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDIL3	NM_005711.5 linkuse as main transcript	c.1342G>A	p.Asp448Asn	missense_variant	11/11	ENST00000296591.10	NP_005702.3	O43854-1
EDIL3	NM_001278642.1 linkuse as main transcript	c.1312G>A	p.Asp438Asn	missense_variant	10/10		NP_001265571.1	O43854-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDIL3	ENST00000296591.10 linkuse as main transcript	c.1342G>A	p.Asp448Asn	missense_variant	11/11	1	NM_005711.5	ENSP00000296591.4		O43854-1
EDIL3	ENST00000380138.3 linkuse as main transcript	c.1312G>A	p.Asp438Asn	missense_variant	10/10	1		ENSP00000369483.3		O43854-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000799

AC:

AN:

250392

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135366

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1460378

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726522

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

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

May 02, 2024

The c.1342G>A (p.D448N) alteration is located in exon 11 (coding exon 11) of the EDIL3 gene. This alteration results from a G to A substitution at nucleotide position 1342, causing the aspartic acid (D) at amino acid position 448 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

0.092

BayesDel_addAF

Benign

-0.054

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.51

D;.

Eigen

Benign

-0.015

Eigen_PC

Benign

0.079

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.83

T;T

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.27

T;T

MetaSVM

Uncertain

0.67

MutationAssessor

Benign

1.6

L;.

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.090

N;N

REVEL

Uncertain

0.33

Sift

Benign

0.35

T;T

Sift4G

Benign

0.090

T;T

Polyphen

0.83

P;B

Vest4

0.11

MutPred

0.61

Gain of catalytic residue at D448 (P = 0.0252);.;

MVP

1.0

MPC

0.25

ClinPred

0.21

GERP RS

3.8

Varity_R

0.094

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over