rs759493890
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 3P and 5B. PM5PP2BP6BS2
The NM_000264.5(PTCH1):c.1324G>T(p.Val442Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V442E) has been classified as Pathogenic.
Frequency
Consequence
NM_000264.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.1324G>T | p.Val442Leu | missense_variant | 9/24 | ENST00000331920.11 | |
PTCH1 | NM_001083603.3 | c.1321G>T | p.Val441Leu | missense_variant | 9/24 | ENST00000437951.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.1324G>T | p.Val442Leu | missense_variant | 9/24 | 5 | NM_000264.5 | A2 | |
PTCH1 | ENST00000437951.6 | c.1321G>T | p.Val441Leu | missense_variant | 9/24 | 5 | NM_001083603.3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251486Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135918
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461886Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727244
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Basal cell carcinoma, susceptibility to, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 17, 2023 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 11, 2023 | The p.V442L variant (also known as c.1324G>T), located in coding exon 9 of the PTCH1 gene, results from a G to T substitution at nucleotide position 1324. The valine at codon 442 is replaced by leucine, an amino acid with highly 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 22, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at