3-89340942-T-C
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_005233.6(EPHA3):āc.841T>Cā(p.Leu281Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,613,326 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 Likely benign (no stars).
Frequency
Genomes: š 0.000053 ( 0 hom., cov: 32)
Exomes š: 0.000028 ( 0 hom. )
Consequence
EPHA3
NM_005233.6 synonymous
NM_005233.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.53
Genes affected
EPHA3 (HGNC:3387): (EPH receptor A3) 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. This gene encodes a protein that binds ephrin-A ligands. Two alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 3-89340942-T-C is Benign according to our data. Variant chr3-89340942-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3059008.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=1.53 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EPHA3 | NM_005233.6 | c.841T>C | p.Leu281Leu | synonymous_variant | 4/17 | ENST00000336596.7 | NP_005224.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EPHA3 | ENST00000336596.7 | c.841T>C | p.Leu281Leu | synonymous_variant | 4/17 | 1 | NM_005233.6 | ENSP00000337451.2 | ||
EPHA3 | ENST00000494014.1 | c.841T>C | p.Leu281Leu | synonymous_variant | 4/17 | 1 | ENSP00000419190.1 | |||
EPHA3 | ENST00000452448.6 | c.841T>C | p.Leu281Leu | synonymous_variant | 4/7 | 1 | ENSP00000399926.2 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152198Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000136 AC: 34AN: 249994Hom.: 0 AF XY: 0.000148 AC XY: 20AN XY: 135102
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GnomAD4 exome AF: 0.0000281 AC: 41AN: 1461010Hom.: 0 Cov.: 31 AF XY: 0.0000413 AC XY: 30AN XY: 726802
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GnomAD4 genome AF: 0.0000525 AC: 8AN: 152316Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74484
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
EPHA3-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | May 02, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
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Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at