rs374370759
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_181882.3(PRX):c.3853G>A(p.Gly1285Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000275 in 1,599,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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.3853G>A | p.Gly1285Arg | missense_variant | 7/7 | ENST00000324001.8 | |
PRX | NM_001411127.1 | c.4138G>A | p.Gly1380Arg | missense_variant | 7/7 | ||
PRX | XM_017027047.2 | c.3751G>A | p.Gly1251Arg | missense_variant | 4/4 | ||
PRX | NM_020956.2 | c.*4058G>A | 3_prime_UTR_variant | 6/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRX | ENST00000324001.8 | c.3853G>A | p.Gly1285Arg | missense_variant | 7/7 | 1 | NM_181882.3 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152166Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000276 AC: 40AN: 1446890Hom.: 0 Cov.: 33 AF XY: 0.0000250 AC XY: 18AN XY: 719046
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152166Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74324
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 27, 2022 | The c.3853G>A (p.G1285R) alteration is located in exon 7 (coding exon 4) of the PRX gene. This alteration results from a G to A substitution at nucleotide position 3853, causing the glycine (G) at amino acid position 1285 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Charcot-Marie-Tooth disease type 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2021 | This sequence change replaces glycine with arginine at codon 1285 of the PRX protein (p.Gly1285Arg). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). 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: 476968). 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"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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