rs863224653
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_000264.5(PTCH1):c.3347T>A(p.Val1116Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000322 in 1,613,956 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.3347T>A | p.Val1116Glu | missense_variant | Exon 20 of 24 | 5 | NM_000264.5 | ENSP00000332353.6 | ||
PTCH1 | ENST00000437951.6 | c.3344T>A | p.Val1115Glu | missense_variant | Exon 20 of 24 | 5 | NM_001083603.3 | ENSP00000389744.2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152208Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 251020Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135740
GnomAD4 exome AF: 0.0000349 AC: 51AN: 1461748Hom.: 0 Cov.: 31 AF XY: 0.0000303 AC XY: 22AN XY: 727174
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152208Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74374
ClinVar
Submissions by phenotype
not provided Uncertain:2
The PTCH1 c.3347T>A (p.Val1116Glu) variant has not been reported in individuals with PTCH1-related conditions in the published literature. The frequency of this variant in the general population, 0.000026 (3/113436 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant. -
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 29641532) -
Hereditary cancer-predisposing syndrome Uncertain:1
The p.V1116E variant (also known as c.3347T>A), located in coding exon 20 of the PTCH1 gene, results from a T to A substitution at nucleotide position 3347. The valine at codon 1116 is replaced by glutamic acid, an amino acid with dissimilar properties. This amino acid position is not well 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
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at