rs104894451
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000270.4(PNP):c.701G>A(p.Arg234Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,614,086 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000270.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152208Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000477 AC: 12AN: 251482Hom.: 0 AF XY: 0.0000441 AC XY: 6AN XY: 135916
GnomAD4 exome AF: 0.0000315 AC: 46AN: 1461878Hom.: 0 Cov.: 31 AF XY: 0.0000303 AC XY: 22AN XY: 727240
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152208Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74358
ClinVar
Submissions by phenotype
Purine-nucleoside phosphorylase deficiency Uncertain:1
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 234 of the PNP protein (p.Arg234Gln). This variant is present in population databases (rs104894451, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with PNP-related conditions. ClinVar contains an entry for this variant (Variation ID: 1000043). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Arg234 amino acid residue in PNP. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 1384322, 9067751, 22132981). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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