Variant 5-84180485-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4

The NM_005711.5(EDIL3):c.263C>T(p.Thr88Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000311 in 1,606,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

EDIL3
NM_005711.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.09

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 made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM1

In a glycosylation_site O-linked (Fuc...) threonine (size 0) in uniprot entity EDIL3_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37796342).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EDIL3	NM_005711.5 linkuse as main transcript	c.263C>T	p.Thr88Ile	missense_variant	4/11	ENST00000296591.10
EDIL3	NM_001278642.1 linkuse as main transcript	c.233C>T	p.Thr78Ile	missense_variant	3/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EDIL3	ENST00000296591.10 linkuse as main transcript	c.263C>T	p.Thr88Ile	missense_variant	4/11	1	NM_005711.5	P1	O43854-1
EDIL3	ENST00000380138.3 linkuse as main transcript	c.233C>T	p.Thr78Ile	missense_variant	3/10	1			O43854-2
EDIL3	ENST00000507663.1 linkuse as main transcript	n.181C>T		non_coding_transcript_exon_variant	2/4	4

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00000409

AC:

AN:

244756

Hom.:

AF XY:

0.00

AC XY:

AN XY:

132240

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:

0.0000342

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1454792

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723500

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:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000333

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152138

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.0000364

Hom.:

Bravo

AF:

0.0000416

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

Jul 08, 2021

The c.263C>T (p.T88I) alteration is located in exon 4 (coding exon 4) of the EDIL3 gene. This alteration results from a C to T substitution at nucleotide position 263, causing the threonine (T) at amino acid position 88 to be replaced by an isoleucine (I). 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

0.058

BayesDel_addAF

Benign

-0.032

BayesDel_noAF

Benign

-0.28

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Uncertain

0.52

D;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.090

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.85

T;T

M_CAP

Benign

0.033

MetaRNN

Benign

0.38

T;T

MetaSVM

Benign

-0.29

MutationAssessor

Benign

0.66

N;.

MutationTaster

Benign

0.91

D;D

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.23

Sift

Benign

0.39

T;T

Sift4G

Benign

0.23

T;T

Polyphen

0.0

B;B

Vest4

0.25

MutPred

0.66

Loss of glycosylation at T88 (P = 0.0053);.;

MVP

0.89

MPC

0.28

ClinPred

0.25

GERP RS

4.5

Varity_R

0.13

gMVP

0.50

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

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