5-84254102-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005711.5(EDIL3):c.178T>G(p.Ser60Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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: 4.26

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34282142).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EDIL3	NM_005711.5	c.178T>G	p.Ser60Ala	missense_variant	2/11	ENST00000296591.10
EDIL3	NM_001278642.1	c.178T>G	p.Ser60Ala	missense_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EDIL3	ENST00000296591.10	c.178T>G	p.Ser60Ala	missense_variant	2/11	1	NM_005711.5	P1
EDIL3	ENST00000380138.3	c.178T>G	p.Ser60Ala	missense_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

Nov 21, 2023

The c.178T>G (p.S60A) alteration is located in exon 2 (coding exon 2) of the EDIL3 gene. This alteration results from a T to G substitution at nucleotide position 178, causing the serine (S) at amino acid position 60 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	0.083
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
Cadd	Benign	22
Dann	Uncertain	0.99
DEOGEN2	Benign	0.21	T;.
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.16	T;T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.34	T;T
MetaSVM	Uncertain	0.70	D
MutationAssessor	Benign	1.9	L;L
MutationTaster	Benign	0.95	D;D
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.0	N;N
REVEL	Uncertain	0.38
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.038	D;D
Polyphen		0.042	B;P
Vest4		0.40
MutPred		0.28		Gain of catalytic residue at S60 (P = 0.0448);Gain of catalytic residue at S60 (P = 0.0448);
MVP		0.93
MPC		0.23
ClinPred		0.79	D
GERP RS		5.6
Varity_R		0.40
gMVP		0.14

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-83549920;