NM_005233.6:c.1306+16016A>G

Variant names:

• chr3-89358106-A-G
• rs9842599
• NM_005233.6:c.1306+16016A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005233.6(EPHA3):​c.1306+16016A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 150,784 control chromosomes in the GnomAD database, including 7,249 homozygotes. 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: 𝑓 0.28 (7249 hom., cov: 31)
• Consequence: EPHA3 NM_005233.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288
• Publications: 6 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005233.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHA3	NM_005233.6	MANE Select	c.1306+16016A>G		intron	N/A	NP_005224.2
	EPHA3	NM_001410778.1		c.1306+16016A>G		intron	N/A	NP_001397707.1	C9JXA2
	EPHA3	NM_182644.3		c.1306+16016A>G		intron	N/A	NP_872585.1	P29320-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHA3	ENST00000336596.7	TSL:1 MANE Select	c.1306+16016A>G		intron	N/A	ENSP00000337451.2	P29320-1
	EPHA3	ENST00000494014.1	TSL:1	c.1306+16016A>G		intron	N/A	ENSP00000419190.1	C9JXA2
	EPHA3	ENST00000452448.6	TSL:1	c.1306+16016A>G		intron	N/A	ENSP00000399926.2	P29320-2

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42546 AN: 150664 Hom.: 7243 Cov.: 31

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.0946

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.129

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.242

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.282 AC: 42572 AN: 150784 Hom.: 7249 Cov.: 31 AF XY: 0.279 AC XY: 20527 AN XY: 73668

African (AFR) AF: 0.330 AC: 13650 AN: 41324

American (AMR) AF: 0.234 AC: 3516 AN: 15044

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 531 AN: 3454

East Asian (EAS) AF: 0.102 AC: 525 AN: 5156

South Asian (SAS) AF: 0.0944 AC: 454 AN: 4808

European-Finnish (FIN) AF: 0.377 AC: 3904 AN: 10364

Middle Eastern (MID) AF: 0.122 AC: 35 AN: 288

European-Non Finnish (NFE) AF: 0.288 AC: 19378 AN: 67344

Other (OTH) AF: 0.240 AC: 501 AN: 2090

Alfa AF: 0.274 Hom.: 8343

Bravo AF: 0.278

Asia WGS AF: 0.104 AC: 359 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.51
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9842599; hg19: chr3-89407256;