17-8393268-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001146684.3(RNF222):c.194G>A(p.Arg65His) variant causes a missense change. The variant allele was found at a frequency of 0.00000429 in 1,399,024 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. R65C) has been classified as Uncertain significance.
Frequency
Consequence
NM_001146684.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RNF222 | NM_001146684.3 | c.194G>A | p.Arg65His | missense_variant | Exon 3 of 3 | ENST00000399398.3 | NP_001140156.1 | |
RNF222 | XM_011523978.4 | c.194G>A | p.Arg65His | missense_variant | Exon 3 of 3 | XP_011522280.1 | ||
RNF222 | XM_011523980.4 | c.194G>A | p.Arg65His | missense_variant | Exon 2 of 2 | XP_011522282.1 | ||
RNF222 | XM_011523981.4 | c.194G>A | p.Arg65His | missense_variant | Exon 2 of 2 | XP_011522283.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000650 AC: 1AN: 153924Hom.: 0 AF XY: 0.0000122 AC XY: 1AN XY: 81834
GnomAD4 exome AF: 0.00000429 AC: 6AN: 1399024Hom.: 0 Cov.: 34 AF XY: 0.00000435 AC XY: 3AN XY: 690032
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.194G>A (p.R65H) 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 194, causing the arginine (R) at amino acid position 65 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