9-95508252-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 3P and 3B. PM2PP2BP4_ModerateBP6
The NM_000264.5(PTCH1):c.110G>A(p.Gly37Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000312 in 1,601,446 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. G37A) has been classified as Likely benign.
Frequency
Consequence
NM_000264.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.110G>A | p.Gly37Glu | missense_variant | 1/24 | ENST00000331920.11 | |
PTCH1 | NM_001083603.3 | c.199-1653G>A | intron_variant | ENST00000437951.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.110G>A | p.Gly37Glu | missense_variant | 1/24 | 5 | NM_000264.5 | A2 | |
PTCH1 | ENST00000437951.6 | c.199-1653G>A | intron_variant | 5 | NM_001083603.3 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151702Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000439 AC: 1AN: 227556Hom.: 0 AF XY: 0.00000795 AC XY: 1AN XY: 125836
GnomAD4 exome AF: 0.00000207 AC: 3AN: 1449744Hom.: 0 Cov.: 34 AF XY: 0.00000139 AC XY: 1AN XY: 720720
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151702Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2AN XY: 74084
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 15, 2022 | The p.G37E variant (also known as c.110G>A), located in coding exon 1 of the PTCH1 gene, results from a G to A substitution at nucleotide position 110. The glycine at codon 37 is replaced by glutamic acid, 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
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at