Variant 1-155078994-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_004952.5(EFNA3):c.53T>A(p.Leu18Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000312 in 1,283,242 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: 0.0000031 ( 0 hom. )

Consequence

EFNA3
NM_004952.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.09

Variant links:

Genes affected

EFNA3 (HGNC:3223): (ephrin A3) 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. [provided by RefSeq, Jul 2008]

EFNA3 links:

EFNA4-EFNA3 (HGNC:):

EFNA4-EFNA3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.864

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFNA3	NM_004952.5 linkuse as main transcript	c.53T>A	p.Leu18Gln	missense_variant	1/5	ENST00000368408.4	NP_004943.1
EFNA4-EFNA3	NM_001407761.1 linkuse as main transcript	c.114-6097T>A		intron_variant			NP_001394690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFNA3	ENST00000368408.4 linkuse as main transcript	c.53T>A	p.Leu18Gln	missense_variant	1/5	1	NM_004952.5	ENSP00000357393	P1	P52797-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000312

AC:

AN:

1283242

Hom.:

Cov.:

AF XY:

0.00000476

AC XY:

AN XY:

630890

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:

9.77e-7

Gnomad4 OTH exome

AF:

0.0000573

GnomAD4 genome

Cov.:

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

Mar 04, 2024

The c.53T>A (p.L18Q) alteration is located in exon 1 (coding exon 1) of the EFNA3 gene. This alteration results from a T to A substitution at nucleotide position 53, causing the leucine (L) at amino acid position 18 to be replaced by a glutamine (Q). 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

0.13

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

DANN

Benign

0.96

DEOGEN2

Benign

0.060

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.54

M_CAP

Pathogenic

0.82

MetaRNN

Pathogenic

0.86

MetaSVM

Uncertain

0.28

MutationAssessor

Benign

0.81

MutationTaster

Benign

0.92

D;D;D

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.86

REVEL

Uncertain

0.57

Sift

Benign

0.14

Sift4G

Benign

0.37

Polyphen

0.98

Vest4

0.75

MutPred

0.54

Gain of disorder (P = 0.0534);

MVP

1.0

MPC

1.1

ClinPred

0.53

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.24

gMVP

0.55

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over