NM_014339.7:c.1426G>A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_014339.7(IL17RA):c.1426G>A(p.Gly476Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000685 in 1,606,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G476E) has been classified as Uncertain significance.
Frequency
Consequence
NM_014339.7 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IL17RA | ENST00000319363.11 | c.1426G>A | p.Gly476Arg | missense_variant | Exon 13 of 13 | 1 | NM_014339.7 | ENSP00000320936.6 | ||
IL17RA | ENST00000612619.2 | c.1324G>A | p.Gly442Arg | missense_variant | Exon 12 of 12 | 5 | ENSP00000479970.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152234Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000124 AC: 3AN: 242294Hom.: 0 AF XY: 0.00000757 AC XY: 1AN XY: 132164
GnomAD4 exome AF: 0.00000619 AC: 9AN: 1454142Hom.: 0 Cov.: 61 AF XY: 0.00000414 AC XY: 3AN XY: 723858
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152234Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74372
ClinVar
Submissions by phenotype
Immunodeficiency 51 Uncertain:1
This sequence change replaces glycine with arginine at codon 476 of the IL17RA protein (p.Gly476Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs763589779, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with IL17RA-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. 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