rs1019888019
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP6BS2
The NM_000264.5(PTCH1):āc.149T>Cā(p.Leu50Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000744 in 1,612,006 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. L50M) has been classified as Uncertain significance.
Frequency
Consequence
NM_000264.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.149T>C | p.Leu50Pro | missense_variant | 1/24 | ENST00000331920.11 | |
PTCH1 | NM_001083603.3 | c.199-1614T>C | intron_variant | ENST00000437951.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.149T>C | p.Leu50Pro | missense_variant | 1/24 | 5 | NM_000264.5 | A2 | |
PTCH1 | ENST00000437951.6 | c.199-1614T>C | intron_variant | 5 | NM_001083603.3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151974Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000407 AC: 1AN: 245954Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134296
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1460032Hom.: 0 Cov.: 34 AF XY: 0.00000551 AC XY: 4AN XY: 726378
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151974Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74252
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 17, 2023 | The p.L50P variant (also known as c.149T>C), located in coding exon 1 of the PTCH1 gene, results from a T to C substitution at nucleotide position 149. The leucine at codon 50 is replaced by proline, 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 | Nov 11, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at