18-32037126-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_017831.4(RNF125):āc.175T>Cā(p.Ser59Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,451,086 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S59F) has been classified as Likely benign.
Frequency
Consequence
NM_017831.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RNF125 | NM_017831.4 | c.175T>C | p.Ser59Pro | missense_variant | 2/6 | ENST00000217740.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RNF125 | ENST00000217740.4 | c.175T>C | p.Ser59Pro | missense_variant | 2/6 | 1 | NM_017831.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 30
GnomAD3 exomes AF: 0.0000125 AC: 3AN: 239234Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 129712
GnomAD4 exome AF: 0.00000207 AC: 3AN: 1451086Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 721808
GnomAD4 genome Cov.: 30
ClinVar
Submissions by phenotype
Tenorio syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 09, 2021 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with RNF125-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with proline at codon 59 of the RNF125 protein (p.Ser59Pro). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and proline. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at