rs876657690
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000503.6(EYA1):c.396_406delGCCGTACGGCA(p.Gln132HisfsTer14) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000503.6 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EYA1 | NM_000503.6 | c.396_406delGCCGTACGGCA | p.Gln132HisfsTer14 | frameshift_variant | Exon 6 of 18 | ENST00000340726.8 | NP_000494.2 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Rare genetic deafness Pathogenic:1
The p.Gln132fs variant in EYA1 has not been previously reported in individuals w ith hearing loss or Branchio-oto-renal spectrum disorder. Data from large popula tion studies is insufficient to assess the frequency of this variant. This frame shift variant is predicted to alter the protein's amino acid sequence beginning at position 132 and leads to a premature termination codon 14 amino acids downst ream. This alteration is then predicted to lead to a truncated or absent protein . Heterozygous loss of function of the EYA1 gene is an established disease mecha nism in individuals with Branchio-oto-renal (BOR) syndrome. In summary, this var iant meets our criteria to be classified as pathogenic for BOR syndrome in an au tosomal dominant manner based upon the predicted impact to the protein. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at