chr14-20475153-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_000270.4(PNP):c.553C>T(p.Arg185Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,614,066 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R185H) has been classified 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 4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152180Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251454Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135900
GnomAD4 exome AF: 0.0000274 AC: 40AN: 1461886Hom.: 0 Cov.: 32 AF XY: 0.0000248 AC XY: 18AN XY: 727246
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152180Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74338
ClinVar
Submissions by phenotype
Purine-nucleoside phosphorylase deficiency Uncertain:1
This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 185 of the PNP protein (p.Arg185Cys). This variant is present in population databases (rs373569964, gnomAD 0.006%). 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: 651865). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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