rs765676916
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_181882.3(PRX):āc.256T>Cā(p.Cys86Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000136 in 1,613,960 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 (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C86Y) has been classified as Uncertain significance.
Frequency
Consequence
NM_181882.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRX | NM_181882.3 | c.256T>C | p.Cys86Arg | missense_variant | 6/7 | ENST00000324001.8 | |
PRX | NM_001411127.1 | c.541T>C | p.Cys181Arg | missense_variant | 6/7 | ||
PRX | NM_020956.2 | c.256T>C | p.Cys86Arg | missense_variant | 6/6 | ||
PRX | XM_017027047.2 | c.154T>C | p.Cys52Arg | missense_variant | 3/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRX | ENST00000324001.8 | c.256T>C | p.Cys86Arg | missense_variant | 6/7 | 1 | NM_181882.3 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152160Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000161 AC: 4AN: 248974Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134780
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461800Hom.: 0 Cov.: 34 AF XY: 0.0000193 AC XY: 14AN XY: 727222
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152160Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74326
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease type 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 08, 2022 | This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 86 of the PRX protein (p.Cys86Arg). This variant is present in population databases (rs765676916, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with PRX-related conditions. ClinVar contains an entry for this variant (Variation ID: 575531). 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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