rs1167104933
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PM1PM2PM5PP3_StrongPP5_Very_Strong
The NM_000317.3(PTS):c.73C>G(p.Arg25Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,430,952 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 Likely pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R25Q) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000317.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTS | NM_000317.3 | c.73C>G | p.Arg25Gly | missense_variant | 1/6 | ENST00000280362.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTS | ENST00000280362.8 | c.73C>G | p.Arg25Gly | missense_variant | 1/6 | 1 | NM_000317.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 exomes AF: 0.0000102 AC: 2AN: 195620Hom.: 0 AF XY: 0.00000950 AC XY: 1AN XY: 105248
GnomAD4 exome AF: 6.99e-7 AC: 1AN: 1430952Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1AN XY: 708570
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
6-Pyruvoyl-tetrahydrobiopterin synthase deficiency Pathogenic:3
Likely pathogenic, no assertion criteria provided | clinical testing | Counsyl | Feb 01, 2017 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 30, 2023 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 15, 2023 | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 25 of the PTS protein (p.Arg25Gly). This variant is present in population databases (no rsID available, gnomAD 0.01%). This missense change has been observed in individual(s) with biopterin deficient hyperphenylalanemia (PMID: 9450907, 23138986). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 463153). 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. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at