rs1268527552
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_181882.3(PRX):āc.3416A>Gā(p.His1139Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,609,122 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 (ā ).
Frequency
Consequence
NM_181882.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PRX | NM_181882.3 | c.3416A>G | p.His1139Arg | missense_variant | 7/7 | ENST00000324001.8 | NP_870998.2 | |
PRX | NM_001411127.1 | c.3701A>G | p.His1234Arg | missense_variant | 7/7 | NP_001398056.1 | ||
PRX | XM_017027047.2 | c.3314A>G | p.His1105Arg | missense_variant | 4/4 | XP_016882536.1 | ||
PRX | NM_020956.2 | c.*3621A>G | 3_prime_UTR_variant | 6/6 | NP_066007.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRX | ENST00000324001.8 | c.3416A>G | p.His1139Arg | missense_variant | 7/7 | 1 | NM_181882.3 | ENSP00000326018 | A2 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152074Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000808 AC: 2AN: 247504Hom.: 0 AF XY: 0.00000745 AC XY: 1AN XY: 134286
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1457048Hom.: 0 Cov.: 33 AF XY: 0.00000276 AC XY: 2AN XY: 724920
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152074Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74282
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease type 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 24, 2021 | This sequence change replaces histidine with arginine at codon 1139 of the PRX protein (p.His1139Arg). The histidine residue is weakly conserved and there is a small physicochemical difference between histidine 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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