8-71321749-C-T
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4BS1BS2
The NM_000503.6(EYA1):c.403G>A(p.Gly135Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00007 in 1,614,094 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000503.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EYA1 | NM_000503.6 | c.403G>A | p.Gly135Ser | missense_variant | Exon 6 of 18 | ENST00000340726.8 | NP_000494.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152216Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000637 AC: 16AN: 250992Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135648
GnomAD4 exome AF: 0.0000753 AC: 110AN: 1461760Hom.: 0 Cov.: 31 AF XY: 0.0000743 AC XY: 54AN XY: 727172
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152334Hom.: 0 Cov.: 33 AF XY: 0.0000268 AC XY: 2AN XY: 74490
ClinVar
Submissions by phenotype
not specified Uncertain:1
The p.Gly135Ser variant in EYA1 has been reported in at least Japanese individua l with hearing loss (Miyagawa 2013) and has also been reported in ClinVar (Varia tion ID#225351). This variant has been identified in 0.06% (11/17210) of East As ian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadi nstitute.org; dbSNP rs747476629); however the frequency is not high enough to ru le out a pathogenic role. Computational prediction tools and conservation analys is suggest that the p.Gly135Ser variant may impact the protein, though this info rmation is not predictive enough to determine pathogenicity. In summary, the cli nical significance of the p.Gly135Ser variant is uncertain. ACMG/AMP Criteria ap plied: PP3 -
not provided Uncertain:1
Reported in a patient with branchiootorenal spectrum disorder in published literature (Wu et al., 2019); clinical details for this individual are not available; Reported in multiple patients with hearing loss in published literature (Minyagawa et al., 2013); clinical information for these patients was not available; In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 34666446, 31738409, 23967202, 31581539) -
Branchiootorenal syndrome 1 Uncertain:1
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Branchiootic syndrome 1;C3714941:Otofaciocervical syndrome 1;C4551702:Branchiootorenal syndrome 1 Uncertain:1
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Branchiootic syndrome 1 Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Melnick-Fraser syndrome Benign:1
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Otofaciocervical syndrome 1 Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at