rs1057520012

Variant names:

• chr4-65404419-C-G
• rs1057520012
• NM_001281766.3:c.1748G>C

Your query was ambiguous. Multiple possible variants found:

• chr4-65404419-C-G
• chr4-65404419-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000613740.5(EPHA5):​c.1748G>C​(p.Gly583Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 32)
• Consequence: EPHA5 ENST00000613740.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.76
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2455644).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000613740.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHA5	NM_001281766.3	MANE Select	c.1748G>C	p.Gly583Ala	missense	Exon 8 of 17	NP_001268695.1
	EPHA5	NM_001281765.3		c.1748G>C	p.Gly583Ala	missense	Exon 8 of 18	NP_001268694.1
	EPHA5	NM_004439.8		c.1745G>C	p.Gly582Ala	missense	Exon 8 of 18	NP_004430.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHA5	ENST00000613740.5	TSL:1 MANE Select	c.1748G>C	p.Gly583Ala	missense	Exon 8 of 17	ENSP00000478537.1
	EPHA5	ENST00000622150.4	TSL:1	c.1748G>C	p.Gly583Ala	missense	Exon 8 of 18	ENSP00000480763.1
	EPHA5	ENST00000273854.7	TSL:1	c.1745G>C	p.Gly582Ala	missense	Exon 8 of 18	ENSP00000273854.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.8
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.15
Sift	Benign	0.16	T
Sift4G	Benign	0.22	T
Polyphen		0.034	B
Vest4		0.44
MutPred		0.56		Loss of sheet (P = 0.0043)
MVP		0.38
MPC		0.26
ClinPred		0.84	D
GERP RS		4.9
Varity_R		0.39
gMVP		0.64
Mutation Taster		=59/41	polymorphism

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: rs1057520012; hg19: chr4-66270137;