Variant 4-65348065-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000613740.5(EPHA5):c.2584A>T(p.Thr862Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000619 in 1,453,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

EPHA5
ENST00000613740.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.16

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22324565).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHA5	NM_001281766.3 linkuse as main transcript	c.2584A>T	p.Thr862Ser	missense_variant	14/17	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.2584A>T	p.Thr862Ser	missense_variant	14/17	1	NM_001281766.3	ENSP00000478537	A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000619

AC:

AN:

1453846

Hom.:

Cov.:

AF XY:

0.00000691

AC XY:

AN XY:

723194

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000812

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000626

Hom.:

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

Jan 08, 2024

The c.2647A>T (p.T883S) alteration is located in exon 15 (coding exon 15) of the EPHA5 gene. This alteration results from a A to T substitution at nucleotide position 2647, causing the threonine (T) at amino acid position 883 to be replaced by a serine (S). 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

0.11

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.37

DEOGEN2

Benign

0.10

T;T;.;T;.;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.014

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.45

T;T;T;T;T;T

M_CAP

Benign

0.0044

MetaRNN

Benign

0.22

T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.23

N;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.77

PROVEAN

Benign

0.33

N;.;.;N;N;N

REVEL

Benign

0.11

Sift

Benign

1.0

T;.;.;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T;T

Polyphen

0.0010

B;B;B;.;B;.

Vest4

0.18

MutPred

0.50

Gain of glycosylation at Y879 (P = 0.0165);.;.;.;.;.;

MVP

0.66

MPC

0.21

ClinPred

0.65

GERP RS

5.9

Varity_R

0.29

gMVP

0.60

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