chr14-20472468-C-T
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000270.4(PNP):c.172C>T(p.Arg58Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000688 in 1,613,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000270.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PNP | NM_000270.4 | c.172C>T | p.Arg58Ter | stop_gained | 2/6 | ENST00000361505.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PNP | ENST00000361505.10 | c.172C>T | p.Arg58Ter | stop_gained | 2/6 | 1 | NM_000270.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152170Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000438 AC: 11AN: 251362Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135864
GnomAD4 exome AF: 0.0000718 AC: 105AN: 1461518Hom.: 0 Cov.: 31 AF XY: 0.0000743 AC XY: 54AN XY: 727086
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152170Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74334
ClinVar
Submissions by phenotype
Purine-nucleoside phosphorylase deficiency Pathogenic:5
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Aug 08, 2019 | This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 01, 2001 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Centogene AG - the Rare Disease Company | Dec 16, 2020 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 19, 2022 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jul 11, 2022 | This sequence change creates a premature translational stop signal (p.Arg58*) in the PNP gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PNP are known to be pathogenic (PMID: 24767876). This variant is present in population databases (rs104894460, gnomAD 0.01%). This premature translational stop signal has been observed in individuals with purine nucleoside phosphorylase (PNP) deficiency (PMID: 24767876). ClinVar contains an entry for this variant (Variation ID: 13996). For these reasons, this variant has been classified as Pathogenic. - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Apr 01, 2022 | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 32695102, 33061764, 11453975, 24767876) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at