rs200712908
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PM1PM2PP3_StrongPP5_Very_Strong
The NM_000317.3(PTS):c.317C>T(p.Thr106Met) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000435 in 1,608,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. T106T) has been classified as Likely benign.
Frequency
Consequence
NM_000317.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTS | NM_000317.3 | c.317C>T | p.Thr106Met | missense_variant, splice_region_variant | 6/6 | ENST00000280362.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTS | ENST00000280362.8 | c.317C>T | p.Thr106Met | missense_variant, splice_region_variant | 6/6 | 1 | NM_000317.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000925 AC: 14AN: 151306Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000117 AC: 29AN: 246840Hom.: 0 AF XY: 0.000157 AC XY: 21AN XY: 133828
GnomAD4 exome AF: 0.0000384 AC: 56AN: 1457460Hom.: 0 Cov.: 31 AF XY: 0.0000524 AC XY: 38AN XY: 724666
GnomAD4 genome AF: 0.0000925 AC: 14AN: 151306Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 73810
ClinVar
Submissions by phenotype
6-Pyruvoyl-tetrahydrobiopterin synthase deficiency Pathogenic:5
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 06, 2024 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 106 of the PTS protein (p.Thr106Met). This variant is present in population databases (rs200712908, gnomAD 0.06%). This missense change has been observed in individual(s) with hyperphenylalaninemia (PMID: 11694255, 23138986, 27246466). ClinVar contains an entry for this variant (Variation ID: 552175). 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. - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | May 24, 2017 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 20, 2022 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 24, 2024 | - - |
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2017 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Aug 07, 2019 | Reported previously in association with PTPS deficiency in multiple unrelated patients (Ye et al., 2013; Liu et al., 1998; Leuzzi et al., 2010; Han et al., 2015); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 33234470, 32651154, 30275481, 25304915, 11694255, 20059486, 9450907, 23138986, 17101845, 16364672, 22237589, 11438997, 9222755, 27246466) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at