9-95508175-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_000264.5(PTCH1):c.187G>C(p.Glu63Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,568 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E63D) has been classified as Uncertain significance.
Frequency
Consequence
NM_000264.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.187G>C | p.Glu63Gln | missense_variant | 1/24 | ENST00000331920.11 | |
PTCH1 | NM_001083603.3 | c.199-1576G>C | intron_variant | ENST00000437951.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.187G>C | p.Glu63Gln | missense_variant | 1/24 | 5 | NM_000264.5 | A2 | |
PTCH1 | ENST00000437951.6 | c.199-1576G>C | intron_variant | 5 | NM_001083603.3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 248420Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135070
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460568Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1AN XY: 726636
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Gorlin syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 23, 2020 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with PTCH1-related conditions. This variant is present in population databases (rs781768965, ExAC 0.002%). This sequence change replaces glutamic acid with glutamine at codon 63 of the PTCH1 protein (p.Glu63Gln). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and glutamine. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 23, 2024 | The p.E63Q variant (also known as c.187G>C), located in coding exon 1 of the PTCH1 gene, results from a G to C substitution at nucleotide position 187. The glutamic acid at codon 63 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at