17-8393235-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001146684.3(RNF222):c.227G>A(p.Arg76His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000038 in 1,551,002 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R76C) has been classified as Uncertain significance.
Frequency
Consequence
NM_001146684.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RNF222 | NM_001146684.3 | c.227G>A | p.Arg76His | missense_variant | Exon 3 of 3 | ENST00000399398.3 | NP_001140156.1 | |
RNF222 | XM_011523978.4 | c.227G>A | p.Arg76His | missense_variant | Exon 3 of 3 | XP_011522280.1 | ||
RNF222 | XM_011523980.4 | c.227G>A | p.Arg76His | missense_variant | Exon 2 of 2 | XP_011522282.1 | ||
RNF222 | XM_011523981.4 | c.227G>A | p.Arg76His | missense_variant | Exon 2 of 2 | XP_011522283.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000263 AC: 40AN: 152168Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000459 AC: 7AN: 152394Hom.: 0 AF XY: 0.0000492 AC XY: 4AN XY: 81286
GnomAD4 exome AF: 0.0000136 AC: 19AN: 1398716Hom.: 0 Cov.: 34 AF XY: 0.0000174 AC XY: 12AN XY: 689886
GnomAD4 genome AF: 0.000263 AC: 40AN: 152286Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20AN XY: 74468
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.227G>A (p.R76H) alteration is located in exon 3 (coding exon 1) of the RNF222 gene. This alteration results from a G to A substitution at nucleotide position 227, causing the arginine (R) at amino acid position 76 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at