Genetic Variant EPHA6:p.Lys67Asn (chr3-96814824-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001080448.3(EPHA6):c.201G>C(p.Lys67Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,438,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

EPHA6
NM_001080448.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.10

Publications

0 publications found

Variant links:

Genes affected

EPHA6 (HGNC:19296): (EPH receptor A6) Predicted to enable transmembrane-ephrin receptor activity. Predicted to be involved in axon guidance; positive regulation of kinase activity; and transmembrane receptor protein tyrosine kinase signaling pathway. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

EPHA6 links:

ENSG00000286447 (HGNC:):

ENSG00000286447 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.075609654).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080448.3. 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
	EPHA6	NM_001080448.3	MANE Select	c.201G>C	p.Lys67Asn	missense	Exon 1 of 18	NP_001073917.2	A0A0B4J1T8
	EPHA6	NM_001278301.2		c.201G>C	p.Lys67Asn	missense	Exon 1 of 4	NP_001265230.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EPHA6	ENST00000389672.10	TSL:1 MANE Select	c.201G>C	p.Lys67Asn	missense	Exon 1 of 18	ENSP00000374323.5	A0A0B4J1T8
EPHA6	ENST00000506569.1	TSL:1	c.33G>C	p.Lys11Asn	missense	Exon 1 of 4	ENSP00000425132.1	H0Y9V0
EPHA6	ENST00000470610.6	TSL:2	c.201G>C	p.Lys67Asn	missense	Exon 1 of 5	ENSP00000420598.2	E7EU71

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000485

AC:

AN:

205984

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000344

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.95e-7

AC:

AN:

1438310

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

713390

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32880

American (AMR)

AF:

0.0000246

AC:

AN:

40636

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25770

East Asian (EAS)

AF:

0.00

AC:

AN:

38368

South Asian (SAS)

AF:

0.00

AC:

AN:

83800

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51706

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1099780

Other (OTH)

AF:

0.00

AC:

AN:

59640

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.019

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.38

M_CAP

Benign

0.043

MetaRNN

Benign

0.076

MetaSVM

Benign

-0.98

PhyloP100

1.1

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.090

REVEL

Benign

0.033

Sift

Uncertain

0.012

Sift4G

Benign

0.16

Polyphen

0.0

Vest4

0.24

MutPred

0.26

Loss of ubiquitination at K67 (P = 0.0023)

MVP

0.52

MPC

0.30

ClinPred

0.030

GERP RS

-0.60

PromoterAI

0.065

Neutral

(source)

gMVP

0.11

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over