5-83963213-T-C

Variant names:

• chr5-83963213-T-C
• NM_005711.5:c.1285A>G

Variant summary

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

The NM_005711.5(EDIL3):​c.1285A>G​(p.Lys429Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EDIL3 NM_005711.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.67
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDIL3	NM_005711.5	c.1285A>G	p.Lys429Glu	missense_variant	Exon 10 of 11	ENST00000296591.10	NP_005702.3
EDIL3	NM_001278642.1	c.1255A>G	p.Lys419Glu	missense_variant	Exon 9 of 10		NP_001265571.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDIL3	ENST00000296591.10	c.1285A>G	p.Lys429Glu	missense_variant	Exon 10 of 11	1	NM_005711.5	ENSP00000296591.4
EDIL3	ENST00000380138.3	c.1255A>G	p.Lys419Glu	missense_variant	Exon 9 of 10	1		ENSP00000369483.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1285A>G (p.K429E) alteration is located in exon 10 (coding exon 10) of the EDIL3 gene. This alteration results from a A to G substitution at nucleotide position 1285, causing the lysine (K) at amino acid position 429 to be replaced by a glutamic acid (E). 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	0.30
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.20
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T;.
Eigen	Benign	0.018
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.53	D;D
MetaSVM	Pathogenic	0.84	D
MutationAssessor	Benign	0.81	L;.
PhyloP100		7.7
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-0.44	N;N
REVEL	Uncertain	0.55
Sift	Benign	0.65	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.052	B;P
Vest4		0.70
MutPred		0.43		Loss of ubiquitination at K429 (P = 0.0218);.;
MVP		0.99
MPC		1.1
ClinPred		0.94	D
GERP RS		5.7
Varity_R		0.31
gMVP		0.72
Mutation Taster		=64/36	polymorphism

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

Other links and lift over

hg19: chr5-83259032;