9-95447417-G-C
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_000264.5(PTCH1):āc.3839C>Gā(p.Ser1280Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000414 in 1,450,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign 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. S1280L) has been classified as Likely benign.
Frequency
Consequence
NM_000264.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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.3839C>G | p.Ser1280Trp | missense_variant | Exon 23 of 24 | 5 | NM_000264.5 | ENSP00000332353.6 | ||
PTCH1 | ENST00000437951.6 | c.3836C>G | p.Ser1279Trp | missense_variant | Exon 23 of 24 | 5 | NM_001083603.3 | ENSP00000389744.2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000417 AC: 1AN: 239534Hom.: 0 AF XY: 0.00000766 AC XY: 1AN XY: 130612
GnomAD4 exome AF: 0.00000414 AC: 6AN: 1450538Hom.: 0 Cov.: 33 AF XY: 0.00000416 AC XY: 3AN XY: 720830
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Basal cell nevus syndrome 1 Uncertain:1
The PTCH1 c.3839C>G (p.Ser1280Trp) missense change has a maximum subpopulation frequency of 0.00092% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with nevoid basal cell carcinoma syndrome. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. -
Hereditary cancer-predisposing syndrome Uncertain:1
The p.S1280W variant (also known as c.3839C>G), located in coding exon 23 of the PTCH1 gene, results from a C to G substitution at nucleotide position 3839. The serine at codon 1280 is replaced by tryptophan, an amino acid with highly dissimilar properties. This amino acid position is conserved. 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
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at