rs104894273
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PM1PM2PM5PP3_StrongPP5_Very_Strong
The NM_000317.3(PTS):c.74G>A(p.Arg25Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000699 in 1,430,606 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. R25G) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000317.3 missense
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 |
---|---|---|---|---|---|---|---|
PTS | NM_000317.3 | c.74G>A | p.Arg25Gln | missense_variant | 1/6 | ENST00000280362.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTS | ENST00000280362.8 | c.74G>A | p.Arg25Gln | missense_variant | 1/6 | 1 | NM_000317.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome AF: 6.99e-7 AC: 1AN: 1430606Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1AN XY: 708392
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
6-Pyruvoyl-tetrahydrobiopterin synthase deficiency Pathogenic:3
Pathogenic, no assertion criteria provided | literature only | OMIM | May 01, 1994 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Mar 09, 2021 | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg25 amino acid residue in PTS. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23138986, 9450907). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this variant affects PTS protein function (PMID: 8178819). This variant has been observed in individual(s) with biopterin-deficient hyperphenylalaninemia (PMID: 8178819). ClinVar contains an entry for this variant (Variation ID: 476). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with glutamine at codon 25 of the PTS protein (p.Arg25Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jul 18, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at