rs762382517
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PP2PP3_ModerateBP6
The NM_000264.5(PTCH1):c.926C>T(p.Pro309Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000373 in 1,610,688 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P309P) has been classified as Likely benign.
Frequency
Consequence
NM_000264.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.926C>T | p.Pro309Leu | missense_variant | 6/24 | ENST00000331920.11 | |
PTCH1 | NM_001083603.3 | c.923C>T | p.Pro308Leu | missense_variant | 6/24 | ENST00000437951.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.926C>T | p.Pro309Leu | missense_variant | 6/24 | 5 | NM_000264.5 | A2 | |
PTCH1 | ENST00000437951.6 | c.923C>T | p.Pro308Leu | missense_variant | 6/24 | 5 | NM_001083603.3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000672 AC: 1AN: 148864Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251416Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135892
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461824Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727198
GnomAD4 genome ? AF: 0.00000672 AC: 1AN: 148864Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 72272
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 19, 2024 | The p.P309L variant (also known as c.926C>T), located in coding exon 6 of the PTCH1 gene, results from a C to T substitution at nucleotide position 926. The proline at codon 309 is replaced by leucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. - |
Gorlin syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 19, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at