rs397517919
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_000503.6(EYA1):c.1697_1698insT(p.Lys566AsnfsTer66) variant causes a frameshift, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. K566?) has been classified as Pathogenic.
Frequency
Consequence
NM_000503.6 frameshift, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EYA1 | NM_000503.6 | c.1697_1698insT | p.Lys566AsnfsTer66 | frameshift_variant, splice_region_variant | 17/18 | ENST00000340726.8 | |
LOC105375894 | XR_007060958.1 | n.4743_4744insA | non_coding_transcript_exon_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EYA1 | ENST00000340726.8 | c.1697_1698insT | p.Lys566AsnfsTer66 | frameshift_variant, splice_region_variant | 17/18 | 1 | NM_000503.6 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome Cov.: 28
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Rare genetic deafness Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 28, 2010 | The Lys566fs variant in EYA1 has not been reported in the literature nor previou sly identified by our laboratory. The Lys566fs variant is predicted to cause a f rameshift, which removes the last 26 amino acid residues of the protein and repl aces them with 65 different residues. Due to the substantial predicted impact to the protein, this variant meets our criteria to be classified as pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at