1-22588912-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_020526.5(EPHA8):c.1021G>T(p.Gly341Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,605,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000017 ( 0 hom. )
Consequence
EPHA8
NM_020526.5 missense
NM_020526.5 missense
Scores
4
11
3
Clinical Significance
Conservation
PhyloP100: 9.91
Genes affected
EPHA8 (HGNC:3391): (EPH receptor A8) This gene encodes a member of 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. The protein encoded by this gene functions as a receptor for ephrin A2, A3 and A5 and plays a role in short-range contact-mediated axonal guidance during development of the mammalian nervous system. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.771
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EPHA8 | NM_020526.5 | c.1021G>T | p.Gly341Trp | missense_variant | 5/17 | ENST00000166244.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EPHA8 | ENST00000166244.8 | c.1021G>T | p.Gly341Trp | missense_variant | 5/17 | 2 | NM_020526.5 | P1 | |
EPHA8 | ENST00000374644.8 | c.1021G>T | p.Gly341Trp | missense_variant | 5/5 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152244Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
2
AN:
152244
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00000817 AC: 2AN: 244738Hom.: 0 AF XY: 0.00000753 AC XY: 1AN XY: 132742
GnomAD3 exomes
AF:
AC:
2
AN:
244738
Hom.:
AF XY:
AC XY:
1
AN XY:
132742
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000172 AC: 25AN: 1453616Hom.: 0 Cov.: 30 AF XY: 0.0000152 AC XY: 11AN XY: 722992
GnomAD4 exome
AF:
AC:
25
AN:
1453616
Hom.:
Cov.:
30
AF XY:
AC XY:
11
AN XY:
722992
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152244Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74384
GnomAD4 genome
?
AF:
AC:
2
AN:
152244
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
74384
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ExAC
?
AF:
AC:
1
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 11, 2023 | The c.1021G>T (p.G341W) alteration is located in exon 5 (coding exon 5) of the EPHA8 gene. This alteration results from a G to T substitution at nucleotide position 1021, causing the glycine (G) at amino acid position 341 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MutPred
Loss of disorder (P = 0.0259);Loss of disorder (P = 0.0259);
MVP
MPC
0.87
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at