chr11-112226490-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_000317.3(PTS):c.47G>A(p.Arg16His) variant causes a missense change. The variant allele was found at a frequency of 0.00000315 in 1,586,550 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 Uncertain significance (★).
Frequency
Consequence
NM_000317.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152154Hom.: 0 Cov.: 31
GnomAD4 exome AF: 0.00000209 AC: 3AN: 1434396Hom.: 0 Cov.: 31 AF XY: 0.00000422 AC XY: 3AN XY: 710624
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152154Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74312
ClinVar
Submissions by phenotype
6-Pyruvoyl-tetrahydrobiopterin synthase deficiency Uncertain:1
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 16 of the PTS protein (p.Arg16His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with PTS-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at