9-95467239-G-C
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4_ModerateBP6BS2
The NM_000264.5(PTCH1):āc.2437C>Gā(p.Pro813Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000416 in 1,612,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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. P813R) has been classified as Uncertain significance.
Frequency
Consequence
NM_000264.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.2437C>G | p.Pro813Ala | missense_variant | 15/24 | ENST00000331920.11 | |
PTCH1 | NM_001083603.3 | c.2434C>G | p.Pro812Ala | missense_variant | 15/24 | ENST00000437951.6 | |
LOC100507346 | NR_038982.1 | n.481+19G>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.2437C>G | p.Pro813Ala | missense_variant | 15/24 | 5 | NM_000264.5 | A2 | |
PTCH1 | ENST00000437951.6 | c.2434C>G | p.Pro812Ala | missense_variant | 15/24 | 5 | NM_001083603.3 |
Frequencies
GnomAD3 genomes AF: 0.0000532 AC: 8AN: 150456Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251494Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135922
GnomAD4 exome AF: 0.0000404 AC: 59AN: 1461850Hom.: 0 Cov.: 33 AF XY: 0.0000399 AC XY: 29AN XY: 727224
GnomAD4 genome AF: 0.0000532 AC: 8AN: 150456Hom.: 0 Cov.: 32 AF XY: 0.0000272 AC XY: 2AN XY: 73510
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden | Nov 03, 2021 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 22, 2015 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Gorlin syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 13, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 12, 2018 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at