chr5-83943496-T-C

Variant names:

• chr5-83943496-T-C
• rs765363548
• NM_005711.5:c.1366A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005711.5(EDIL3):​c.1366A>G​(p.Ile456Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,612,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: EDIL3 NM_005711.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.292
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20324707).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDIL3	NM_005711.5	c.1366A>G	p.Ile456Val	missense_variant	Exon 11 of 11	ENST00000296591.10	NP_005702.3
EDIL3	NM_001278642.1	c.1336A>G	p.Ile446Val	missense_variant	Exon 10 of 10		NP_001265571.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDIL3	ENST00000296591.10	c.1366A>G	p.Ile456Val	missense_variant	Exon 11 of 11	1	NM_005711.5	ENSP00000296591.4
EDIL3	ENST00000380138.3	c.1336A>G	p.Ile446Val	missense_variant	Exon 10 of 10	1		ENSP00000369483.3

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 151992 Hom.: 0 Cov.: 32

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 250728 AF XY: 0.0000369

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000530

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000130 AC: 19 AN: 1460742 Hom.: 0 Cov.: 32 AF XY: 0.0000165 AC XY: 12 AN XY: 726706

African (AFR) AF: 0.0000299 AC: 1 AN: 33392

American (AMR) AF: 0.00 AC: 0 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39588

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1111292

Other (OTH) AF: 0.00 AC: 0 AN: 60324

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 151992 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74214

African (AFR) AF: 0.0000241 AC: 1 AN: 41426

American (AMR) AF: 0.00 AC: 0 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5142

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67960

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000450 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.0000546

EpiControl AF: 0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1366A>G (p.I456V) alteration is located in exon 11 (coding exon 11) of the EDIL3 gene. This alteration results from a A to G substitution at nucleotide position 1366, causing the isoleucine (I) at amino acid position 456 to be replaced by a valine (V). 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	0.077
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	9.4
DANN	Benign	0.55
DEOGEN2	Uncertain	0.44	T;.
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.57
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.20	T;T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Benign	-0.69	N;.
PhyloP100		0.29
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.040	N;N
REVEL	Uncertain	0.29
Sift	Benign	0.99	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.17
MutPred		0.57		Gain of MoRF binding (P = 0.1059);.;
MVP		0.47
MPC		0.21
ClinPred		0.029	T
GERP RS		3.3
Varity_R		0.026
gMVP		0.42
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs765363548; hg19: chr5-83239315; COSMIC: COSV56878433;