rs377120922
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PP2PP3BP6
The NM_000264.5(PTCH1):c.2891C>T(p.Pro964Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,222 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P964A) has been classified as Uncertain significance.
Frequency
Consequence
NM_000264.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.2891C>T | p.Pro964Leu | missense_variant | 18/24 | ENST00000331920.11 | |
PTCH1 | NM_001083603.3 | c.2888C>T | p.Pro963Leu | missense_variant | 18/24 | ENST00000437951.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.2891C>T | p.Pro964Leu | missense_variant | 18/24 | 5 | NM_000264.5 | A2 | |
PTCH1 | ENST00000437951.6 | c.2888C>T | p.Pro963Leu | missense_variant | 18/24 | 5 | NM_001083603.3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151866Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000405 AC: 1AN: 247068Hom.: 0 AF XY: 0.00000747 AC XY: 1AN XY: 133914
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461356Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 726914
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151866Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74148
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 01, 2019 | The p.P964L variant (also known as c.2891C>T), located in coding exon 18 of the PTCH1 gene, results from a C to T substitution at nucleotide position 2891. The proline at codon 964 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Gorlin syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 12, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at