chr11-112233179-C-T
Variant summary
Our verdict is Pathogenic. Variant got 15 ACMG points: 15P and 0B. PM1PM2PM5PP3PP5_Very_Strong
The NM_000317.3(PTS):c.260C>T(p.Pro87Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000867 in 1,613,882 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. P87S) has been classified as Pathogenic.
Frequency
Consequence
NM_000317.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTS | NM_000317.3 | c.260C>T | p.Pro87Leu | missense_variant | 5/6 | ENST00000280362.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTS | ENST00000280362.8 | c.260C>T | p.Pro87Leu | missense_variant | 5/6 | 1 | NM_000317.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152132Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251448Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135890
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461750Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727176
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152132Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74322
ClinVar
Submissions by phenotype
6-Pyruvoyl-tetrahydrobiopterin synthase deficiency Pathogenic:5
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 13, 2023 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 87 of the PTS protein (p.Pro87Leu). This variant is present in population databases (rs765406631, gnomAD 0.002%). This missense change has been observed in individual(s) with biopterin deficient hyperphenylalanemia (PMID: 7493990, 10319579, 11388593, 11694255, 19350512). ClinVar contains an entry for this variant (Variation ID: 553829). 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 tolerated. Experimental studies have shown that this missense change affects PTS function (PMID: 7493990, 10319579, 11388593). For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Feb 28, 2024 | - - |
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 20, 2021 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Sep 13, 2017 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at