5-84254086-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_005711.5(EDIL3):c.194T>C(p.Val65Ala) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EDIL3 NM_005711.5 missense, splice_region
• Scores: Splicing: ADA: 0.0003014
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.43

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.756

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EDIL3	NM_005711.5	c.194T>C	p.Val65Ala	missense_variant, splice_region_variant	2/11	ENST00000296591.10
EDIL3	NM_001278642.1	c.194T>C	p.Val65Ala	missense_variant, splice_region_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EDIL3	ENST00000296591.10	c.194T>C	p.Val65Ala	missense_variant, splice_region_variant	2/11	1	NM_005711.5	P1
EDIL3	ENST00000380138.3	c.194T>C	p.Val65Ala	missense_variant, splice_region_variant	2/10	1

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2022

The c.194T>C (p.V65A) alteration is located in exon 2 (coding exon 2) of the EDIL3 gene. This alteration results from a T to C substitution at nucleotide position 194, causing the valine (V) at amino acid position 65 to be replaced by an alanine (A). 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	0.093
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
Cadd	Benign	21
Dann	Benign	0.56
DEOGEN2	Benign	0.13	T;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.64	T;T
M_CAP	Uncertain	0.095	D
MetaRNN	Pathogenic	0.76	D;D
MetaSVM	Uncertain	0.30	D
MutationAssessor	Benign	0.17	N;N
MutationTaster	Benign	1.0	D;N
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.42	N;N
REVEL	Uncertain	0.51
Sift	Uncertain	0.014	D;T
Sift4G	Benign	1.0	T;T
Polyphen		0.92	P;P
Vest4		0.68
MutPred		0.31		Loss of stability (P = 0.0602);Loss of stability (P = 0.0602);
MVP		0.98
MPC		0.31
ClinPred		0.89	D
GERP RS		5.6
Varity_R		0.23
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00030
dbscSNV1_RF	Benign	0.012
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-83549904;