Variant 1-155063928-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_005227.3(EFNA4):c.105T>A(p.Ser35Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000156 in 1,407,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

EFNA4
NM_005227.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0590

Variant links:

Genes affected

EFNA4 (HGNC:3224): (ephrin A4) This gene encodes a member of the ephrin (EPH) family. The ephrins and EPH-related receptors comprise the largest subfamily of receptor protein-tyrosine kinases and have been implicated in mediating developmental events, especially in the nervous system and in erythropoiesis. 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. This gene encodes an EFNA class ephrin that has been implicated in proliferation and metastasis of several types of cancers. [provided by RefSeq, May 2022]

EFNA4 links:

EFNA4-EFNA3 (HGNC:):

EFNA4-EFNA3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.817

BS2

High AC in GnomAdExome4 at 22 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
EFNA4	NM_005227.3 linkuse as main transcript	c.105T>A	p.Ser35Arg	missense_variant	1/4	ENST00000368409.8	NP_005218.1
EFNA4-EFNA3	NM_001407761.1 linkuse as main transcript	c.105T>A	p.Ser35Arg	missense_variant	1/5		NP_001394690.1
DCST1-AS1	NR_040773.1 linkuse as main transcript	n.64A>T		non_coding_transcript_exon_variant	1/4
ADAM15-EFNA4	NR_176418.1 linkuse as main transcript	n.3423T>A		non_coding_transcript_exon_variant	22/26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFNA4	ENST00000368409.8 linkuse as main transcript	c.105T>A	p.Ser35Arg	missense_variant	1/4	1	NM_005227.3	ENSP00000357394		P52798-1
EFNA4	ENST00000359751.8 linkuse as main transcript	c.105T>A	p.Ser35Arg	missense_variant	1/4	1		ENSP00000352789	P2	P52798-2
EFNA4	ENST00000427683.2 linkuse as main transcript	c.105T>A	p.Ser35Arg	missense_variant	1/4	2		ENSP00000414378	A2	P52798-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000551

AC:

AN:

163466

Hom.:

AF XY:

0.0000444

AC XY:

AN XY:

90000

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000731

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000147

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000156

AC:

AN:

1407538

Hom.:

Cov.:

AF XY:

0.0000158

AC XY:

AN XY:

697168

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000603

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.20e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000257

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

Dec 19, 2022

The c.105T>A (p.S35R) alteration is located in exon 1 (coding exon 1) of the EFNA4 gene. This alteration results from a T to A substitution at nucleotide position 105, causing the serine (S) at amino acid position 35 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

Pathogenic

0.92

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.68

D;.;.;.

Eigen

Benign

-0.072

Eigen_PC

Benign

-0.074

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.91

D;D;D;D

M_CAP

Pathogenic

0.70

MetaRNN

Pathogenic

0.82

D;D;D;D

MetaSVM

Uncertain

0.35

MutationAssessor

Uncertain

2.6

M;M;M;.

MutationTaster

Benign

0.99

D;D;D;D

PROVEAN

Uncertain

-3.3

D;D;D;D

REVEL

Uncertain

0.56

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Uncertain

0.0030

D;D;D;D

Polyphen

0.038

B;D;.;.

Vest4

0.51

MutPred

0.84

Gain of MoRF binding (P = 0.0238);Gain of MoRF binding (P = 0.0238);Gain of MoRF binding (P = 0.0238);Gain of MoRF binding (P = 0.0238);

MVP

0.94

MPC

1.1

ClinPred

0.60

GERP RS

0.0067

Varity_R

0.71

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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