rs763350623
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004100.5(EYA4):c.523C>A(p.Pro175Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_004100.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EYA4 | NM_004100.5 | c.523C>A | p.Pro175Thr | missense_variant | 8/20 | ENST00000355286.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EYA4 | ENST00000355286.12 | c.523C>A | p.Pro175Thr | missense_variant | 8/20 | 1 | NM_004100.5 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251362Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135854
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461774Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727198
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Dilated cardiomyopathy 1J Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 21, 2017 | Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. This variant is present in population databases (rs763350623, ExAC 0.03%) but has not been reported in the literature in individuals with a EYA4-related disease. This sequence change replaces proline with threonine at codon 175 of the EYA4 protein (p.Pro175Thr). The proline residue is moderately conserved and there is a small physicochemical difference between proline and threonine. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at