rs1432645175
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000264.5(PTCH1):c.1209T>G(p.Tyr403Ter) variant causes a stop gained 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 (★★). Synonymous variant affecting the same amino acid position (i.e. Y403Y) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000264.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.1209T>G | p.Tyr403Ter | stop_gained | 8/24 | ENST00000331920.11 | |
PTCH1 | NM_001083603.3 | c.1206T>G | p.Tyr402Ter | stop_gained | 8/24 | ENST00000437951.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.1209T>G | p.Tyr403Ter | stop_gained | 8/24 | 5 | NM_000264.5 | A2 | |
PTCH1 | ENST00000437951.6 | c.1206T>G | p.Tyr402Ter | stop_gained | 8/24 | 5 | NM_001083603.3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Gorlin syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Feb 18, 2023 | This sequence change creates a premature translational stop signal (p.Tyr403*) in the PTCH1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PTCH1 are known to be pathogenic (PMID: 16301862, 16419085). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PTCH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 524572). For these reasons, this variant has been classified as Pathogenic. - |
Hereditary cancer-predisposing syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 17, 2020 | The p.Y403* variant (also known as c.1209T>G), located in coding exon 8 of the PTCH1 gene, results from a T to G substitution at nucleotide position 1209. This changes the amino acid from a tyrosine to a stop codon within coding exon 8. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at