11-112226417-CCGAGCACCGCAGACAGCGCCGGGAAGATGAGCA-C
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM2PP5_Very_Strong
The NM_000317.3(PTS):c.-26_7delCGAGCACCGCAGACAGCGCCGGGAAGATGAGCA variant causes a 5 prime UTR truncation, exon loss change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_000317.3 5_prime_UTR_truncation, exon_loss
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PTS | NM_000317.3 | c.-26_7delCGAGCACCGCAGACAGCGCCGGGAAGATGAGCA | p.Met1fs | frameshift_variant, start_lost | Exon 1 of 6 | ENST00000280362.8 | NP_000308.1 | |
PTS | NM_000317.3 | c.-26_7delCGAGCACCGCAGACAGCGCCGGGAAGATGAGCA | 5_prime_UTR_truncation, exon_loss_variant | Exon 1 of 6 | ENST00000280362.8 | NP_000308.1 | ||
PTS | NM_000317.3 | c.-26_7delCGAGCACCGCAGACAGCGCCGGGAAGATGAGCA | upstream_gene_variant | ENST00000280362.8 | NP_000308.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PTS | ENST00000280362.8 | c.-24_9delAGCACCGCAGACAGCGCCGGGAAGATGAGCACG | p.Met1fs | frameshift_variant, start_lost | Exon 1 of 6 | 1 | NM_000317.3 | ENSP00000280362.3 | ||
PTS | ENST00000280362 | c.-24_9delAGCACCGCAGACAGCGCCGGGAAGATGAGCACG | 5_prime_UTR_truncation, exon_loss_variant | Exon 1 of 6 | 1 | NM_000317.3 | ENSP00000280362.3 | |||
PTS | ENST00000280362.8 | c.-26_7delCGAGCACCGCAGACAGCGCCGGGAAGATGAGCA | upstream_gene_variant | 1 | NM_000317.3 | ENSP00000280362.3 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
6-Pyruvoyl-tetrahydrobiopterin synthase deficiency Pathogenic:4
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This sequence change affects the initiator methionine of the PTS mRNA. The next in-frame methionine is located at codon 69. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PTS-related conditions. ClinVar contains an entry for this variant (Variation ID: 1067052). This variant disrupts a region of the PTS protein in which other variant(s) (p.Arg25Gly) have been determined to be pathogenic (PMID: 9450907, 23138986). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.