11-112226444-A-G
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000317.3(PTS):c.1A>G(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_000317.3 start_lost
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
6-Pyruvoyl-tetrahydrobiopterin synthase deficiency Pathogenic:1
For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the PTS protein in which other variant(s) (p.Thr67Met) have been determined to be pathogenic (PMID: 11438997, 11694255, 16850690, 22237589). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 1067348). Disruption of the initiator codon has been observed in individual(s) with tetrahydrobiopterin-deficient hyperphenylalaninemia (PMID: 22237589, 29499199, 30926181). This variant is not present in population databases (gnomAD no frequency). This sequence change affects the initiator methionine of the PTS mRNA. The next in-frame methionine is located at codon 69. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.