Variant 5-107670574-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_ModerateBS2

The NM_001962.3(EFNA5):c.40C>T(p.Leu14Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000345 in 1,450,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

EFNA5
NM_001962.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.71

Variant links:

Genes affected

EFNA5 (HGNC:3225): (ephrin A5) Ephrin-A5, a member of the ephrin gene family, prevents axon bundling in cocultures of cortical neurons with astrocytes, a model of late stage nervous system development and differentiation. The EPH and EPH-related receptors comprise the largest subfamily of receptor protein-tyrosine kinases and have been implicated in mediating developmental events, particularly in the nervous system. EPH receptors typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin ligands and receptors have been named by the Eph Nomenclature Committee (1997). Based on their structures and sequence relationships, ephrins are divided into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. The Eph family of receptors are similarly divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. [provided by RefSeq, Jul 2008]

EFNA5 links:

EFNA5 (HGNC:):

EFNA5 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26074624).

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFNA5	NM_001962.3 linkuse as main transcript	c.40C>T	p.Leu14Phe	missense_variant	1/5	ENST00000333274.11	NP_001953.1	P52803
EFNA5	NM_001410773.1 linkuse as main transcript	c.40C>T	p.Leu14Phe	missense_variant	1/4		NP_001397702.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
EFNA5	ENST00000333274.11 linkuse as main transcript	c.40C>T	p.Leu14Phe	missense_variant	1/5	1	NM_001962.3	ENSP00000328777.6	P52803
EFNA5	ENST00000504941.1 linkuse as main transcript	n.312C>T		non_coding_transcript_exon_variant	1/2	1
EFNA5	ENST00000509503.1 linkuse as main transcript	c.40C>T	p.Leu14Phe	missense_variant	1/4	5		ENSP00000426989.1	D6RDV5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000130

AC:

AN:

230712

Hom.:

AF XY:

0.00000802

AC XY:

AN XY:

124682

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000599

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000360

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000345

AC:

AN:

1450296

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

720504

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000908

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000825

AC:

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

Aug 19, 2024

The c.40C>T (p.L14F) alteration is located in exon 1 (coding exon 1) of the EFNA5 gene. This alteration results from a C to T substitution at nucleotide position 40, causing the leucine (L) at amino acid position 14 to be replaced by a phenylalanine (F). 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

0.074

BayesDel_addAF

Benign

0.0021

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

T;.

Eigen

Benign

-0.066

Eigen_PC

Benign

0.039

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.77

T;T

M_CAP

Pathogenic

0.45

MetaRNN

Benign

0.26

T;T

MetaSVM

Uncertain

0.50

MutationAssessor

Uncertain

2.1

M;.

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.90

N;N

REVEL

Uncertain

0.39

Sift

Uncertain

0.027

D;D

Sift4G

Uncertain

0.054

T;D

Polyphen

0.57

P;B

Vest4

0.31

MutPred

0.42

Gain of helix (P = 0.132);Gain of helix (P = 0.132);

MVP

0.62

MPC

0.97

ClinPred

0.33

GERP RS

3.7

Varity_R

0.16

gMVP

0.44

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