Genetic Variant EPHA6:p.Gln73Lys (chr3-96814840-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001080448.3(EPHA6):c.217C>A(p.Gln73Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q73E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EPHA6
NM_001080448.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.856

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.049915314).

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.217C>A	p.Gln73Lys	missense	Exon 1 of 18	NP_001073917.2	A0A0B4J1T8
	EPHA6	NM_001278301.2		c.217C>A	p.Gln73Lys	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.217C>A	p.Gln73Lys	missense	Exon 1 of 18	ENSP00000374323.5	A0A0B4J1T8
EPHA6	ENST00000506569.1	TSL:1	c.49C>A	p.Gln17Lys	missense	Exon 1 of 4	ENSP00000425132.1	H0Y9V0
EPHA6	ENST00000470610.6	TSL:2	c.217C>A	p.Gln73Lys	missense	Exon 1 of 5	ENSP00000420598.2	E7EU71

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1425176

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

705760

African (AFR)

AF:

0.00

AC:

AN:

32450

American (AMR)

AF:

0.00

AC:

AN:

38404

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25576

East Asian (EAS)

AF:

0.00

AC:

AN:

37450

South Asian (SAS)

AF:

0.00

AC:

AN:

82322

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50876

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1093200

Other (OTH)

AF:

0.00

AC:

AN:

59172

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

3.5

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.019

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.54

M_CAP

Benign

0.033

MetaRNN

Benign

0.050

MetaSVM

Benign

-1.0

PhyloP100

0.86

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.28

REVEL

Benign

0.013

Sift

Benign

0.59

Sift4G

Benign

0.13

Polyphen

0.0010

Vest4

0.23

MutPred

0.14

Gain of ubiquitination at Q73 (P = 0.0048)

MVP

0.52

MPC

0.33

ClinPred

0.025

GERP RS

2.2

PromoterAI

0.0089

Neutral

(source)

gMVP

0.079

Mutation Taster

=97/3

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