Variant 4-65324131-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001281766.3(EPHA5):c.3034G>A(p.Gly1012Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000201 in 1,608,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

EPHA5
NM_001281766.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.31

Variant links:

Genes affected

EPHA5 (HGNC:3389): (EPH receptor A5) This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Aug 2013]

EPHA5 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06623399).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHA5	NM_001281766.3 linkuse as main transcript	c.3034G>A	p.Gly1012Arg	missense_variant	17/17	ENST00000613740.5	NP_001268695.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHA5	ENST00000613740.5 linkuse as main transcript	c.3034G>A	p.Gly1012Arg	missense_variant	17/17	1	NM_001281766.3	ENSP00000478537	A2

Frequencies

GnomAD3 genomes

AF:

0.000152

AC:

AN:

151422

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000726

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000463

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000217

AC:

AN:

249168

Hom.:

AF XY:

0.000238

AC XY:

AN XY:

134714

show subpopulations

Gnomad AFR exome

AF:

0.000125

Gnomad AMR exome

AF:

0.000205

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000295

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000275

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000206

AC:

300

AN:

1456640

Hom.:

Cov.:

AF XY:

0.000210

AC XY:

152

AN XY:

724704

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000163

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000236

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000152

AC:

AN:

151540

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

74062

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000462

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000148

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000209

Hom.:

Bravo

AF:

0.000189

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000165

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000219

EpiControl

AF:

0.000299

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

Jun 18, 2021

The c.3097G>A (p.G1033R) alteration is located in exon 18 (coding exon 18) of the EPHA5 gene. This alteration results from a G to A substitution at nucleotide position 3097, causing the glycine (G) at amino acid position 1033 to be replaced by an arginine (R). 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

0.20

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.71

DEOGEN2

Benign

0.051

T;T;.;T;.

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.045

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.82

T;T;T;T;T

M_CAP

Benign

0.035

MetaRNN

Benign

0.066

T;T;T;T;T

MetaSVM

Benign

-0.70

MutationAssessor

Benign

0.47

N;.;.;.;.

MutationTaster

Benign

0.97

D;D;D

PrimateAI

Uncertain

0.73

PROVEAN

Benign

0.010

N;.;.;N;N

REVEL

Benign

0.088

Sift

Benign

0.16

T;.;.;T;T

Sift4G

Benign

0.52

T;T;T;T;T

Polyphen

0.80

P;D;B;.;D

Vest4

0.16

MutPred

0.37

Gain of MoRF binding (P = 3e-04);.;.;.;.;

MVP

0.83

MPC

0.52

ClinPred

0.051

GERP RS

4.4

Varity_R

0.10

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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