rs761769929
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_181882.3(PRX):c.2816C>T(p.Ser939Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000142 in 1,614,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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. S939W) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRX | NM_181882.3 | c.2816C>T | p.Ser939Leu | missense_variant | 7/7 | ENST00000324001.8 | |
PRX | NM_001411127.1 | c.3101C>T | p.Ser1034Leu | missense_variant | 7/7 | ||
PRX | XM_017027047.2 | c.2714C>T | p.Ser905Leu | missense_variant | 4/4 | ||
PRX | NM_020956.2 | c.*3021C>T | 3_prime_UTR_variant | 6/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRX | ENST00000324001.8 | c.2816C>T | p.Ser939Leu | missense_variant | 7/7 | 1 | NM_181882.3 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152170Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251428Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135902
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461892Hom.: 0 Cov.: 99 AF XY: 0.00000963 AC XY: 7AN XY: 727246
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152288Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74470
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Molecular Genetics Laboratory, London Health Sciences Centre | - | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Dec 09, 2019 | - - |
Charcot-Marie-Tooth disease type 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 12, 2022 | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 939 of the PRX protein (p.Ser939Leu). This variant is present in population databases (rs761769929, gnomAD 0.03%). This missense change has been observed in individual(s) with clinical features of Charcot-Marie-Tooth disease (PMID: 32376792). ClinVar contains an entry for this variant (Variation ID: 917234). 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