rs1060502265
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_000264.5(PTCH1):c.3748C>T(p.Pro1250Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,614,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000264.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.3748C>T | p.Pro1250Ser | missense_variant | Exon 22 of 24 | 5 | NM_000264.5 | ENSP00000332353.6 | ||
PTCH1 | ENST00000437951.6 | c.3745C>T | p.Pro1249Ser | missense_variant | Exon 22 of 24 | 5 | NM_001083603.3 | ENSP00000389744.2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152240Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250668Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135660
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461844Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727224
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152240Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74374
ClinVar
Submissions by phenotype
Basal cell carcinoma, susceptibility to, 1 Uncertain:1
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Hereditary cancer-predisposing syndrome Uncertain:1
The p.P1250S variant (also known as c.3748C>T), located in coding exon 22 of the PTCH1 gene, results from a C to T substitution at nucleotide position 3748. The proline at codon 1250 is replaced by serine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Gorlin syndrome Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at