Variant chr1-37718400-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001099439.2(EPHA10):c.2999A>C(p.Gln1000Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,460,244 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

EPHA10
NM_001099439.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.10

Variant links:

Genes affected

EPHA10 (HGNC:19987): (EPH receptor A10) Ephrin receptors, the largest subfamily of receptor tyrosine kinases (RTKs), and their ephrin ligands are important mediators of cell-cell communication regulating cell attachment, shape, and mobility in neuronal and epithelial cells (Aasheim et al., 2005 [PubMed 15777695]). See MIM 179610 for additional background on Eph receptors and ephrins.[supplied by OMIM, Mar 2008]

EPHA10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.33579943).

BS2

High AC in GnomAdExome4 at 25 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHA10	NM_001099439.2 link	c.2999A>C	p.Gln1000Pro	missense_variant	17/17	ENST00000373048.9	NP_001092909.1	Q5JZY3-1Q4G0R4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
EPHA10	ENST00000373048.9 link	c.2999A>C	p.Gln1000Pro	missense_variant	17/17	5	NM_001099439.2	ENSP00000362139.4	Q5JZY3-1
EPHA10	ENST00000432874.7 link	n.*900A>C		non_coding_transcript_exon_variant	13/16	5		ENSP00000436425.1	H0YER4
EPHA10	ENST00000432874.7 link	n.*900A>C		3_prime_UTR_variant	13/16	5		ENSP00000436425.1	H0YER4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1460244

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

726400

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:

0.0000225

Gnomad4 OTH exome

AF:

0.00

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

Dec 10, 2024

The c.2999A>C (p.Q1000P) alteration is located in exon 17 (coding exon 17) of the EPHA10 gene. This alteration results from a A to C substitution at nucleotide position 2999, causing the glutamine (Q) at amino acid position 1000 to be replaced by a proline (P). 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

0.14

BayesDel_addAF

Benign

-0.043

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.034

T;T

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.60

T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.34

T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

2.0

.;M

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.14

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.0060

D;D

Polyphen

0.97

.;D

Vest4

0.76

MutPred

0.50

Loss of helix (P = 0.0033);Loss of helix (P = 0.0033);

MVP

0.72

MPC

0.13

ClinPred

0.89

GERP RS

4.9

Varity_R

0.65

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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