Variant 3-89342065-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_005233.6(EPHA3):c.1281G>A(p.Ala427=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00488 in 1,609,542 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0037 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0050 ( 25 hom. )

Consequence

EPHA3
NM_005233.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -1.23

Variant links:

Genes affected

EPHA3 (HGNC:3387): (EPH receptor A3) 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. This gene encodes a protein that binds ephrin-A ligands. Two alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jul 2008]

EPHA3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 3-89342065-G-A is Benign according to our data. Variant chr3-89342065-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2653989.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.23 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 25 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHA3	NM_005233.6 linkuse as main transcript	c.1281G>A	p.Ala427=	synonymous_variant	5/17	ENST00000336596.7	NP_005224.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHA3	ENST00000336596.7 linkuse as main transcript	c.1281G>A	p.Ala427=	synonymous_variant	5/17	1	NM_005233.6	ENSP00000337451	P1	P29320-1
EPHA3	ENST00000494014.1 linkuse as main transcript	c.1281G>A	p.Ala427=	synonymous_variant	5/17	1		ENSP00000419190
EPHA3	ENST00000452448.6 linkuse as main transcript	c.1281G>A	p.Ala427=	synonymous_variant	5/7	1		ENSP00000399926		P29320-2

Frequencies

GnomAD3 genomes

AF:

0.00372

AC:

550

AN:

147736

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00100

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00198

Gnomad ASJ

AF:

0.000584

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00454

Gnomad FIN

AF:

0.00990

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00525

Gnomad OTH

AF:

0.00348

GnomAD3 exomes

AF:

0.00499

AC:

1242

AN:

248954

Hom.:

AF XY:

0.00512

AC XY:

690

AN XY:

134722

show subpopulations

Gnomad AFR exome

AF:

0.000985

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00546

Gnomad FIN exome

AF:

0.00973

Gnomad NFE exome

AF:

0.00693

Gnomad OTH exome

AF:

0.00343

GnomAD4 exome

AF:

0.00500

AC:

7311

AN:

1461688

Hom.:

Cov.:

AF XY:

0.00502

AC XY:

3649

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.000986

Gnomad4 AMR exome

AF:

0.00143

Gnomad4 ASJ exome

AF:

0.00218

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00580

Gnomad4 FIN exome

AF:

0.00910

Gnomad4 NFE exome

AF:

0.00535

Gnomad4 OTH exome

AF:

0.00348

GnomAD4 genome

AF:

0.00371

AC:

549

AN:

147854

Hom.:

Cov.:

AF XY:

0.00400

AC XY:

287

AN XY:

71792

show subpopulations

Gnomad4 AFR

AF:

0.00100

Gnomad4 AMR

AF:

0.00198

Gnomad4 ASJ

AF:

0.000584

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00432

Gnomad4 FIN

AF:

0.00990

Gnomad4 NFE

AF:

0.00525

Gnomad4 OTH

AF:

0.00344

Alfa

AF:

0.00465

Hom.:

Bravo

AF:

0.00325

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

EPHA3: BP4, BP7, BS2 -

EPHA3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 30, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.6

DANN

Benign

0.65

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

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