rs149258400
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2
The NM_000264.5(PTCH1):c.2173C>T(p.Pro725Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00088 in 1,614,158 control chromosomes in the GnomAD database, including 7 homozygotes. 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 Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P725R) has been classified as Likely benign.
Frequency
Consequence
NM_000264.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.2173C>T | p.Pro725Ser | missense_variant | 14/24 | ENST00000331920.11 | |
PTCH1 | NM_001083603.3 | c.2170C>T | p.Pro724Ser | missense_variant | 14/24 | ENST00000437951.6 | |
LOC100507346 | NR_038982.1 | n.766G>A | non_coding_transcript_exon_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.2173C>T | p.Pro725Ser | missense_variant | 14/24 | 5 | NM_000264.5 | A2 | |
PTCH1 | ENST00000437951.6 | c.2170C>T | p.Pro724Ser | missense_variant | 14/24 | 5 | NM_001083603.3 |
Frequencies
GnomAD3 genomes AF: 0.00103 AC: 156AN: 152156Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000915 AC: 230AN: 251484Hom.: 0 AF XY: 0.00101 AC XY: 137AN XY: 135914
GnomAD4 exome AF: 0.000865 AC: 1265AN: 1461884Hom.: 7 Cov.: 33 AF XY: 0.000910 AC XY: 662AN XY: 727242
GnomAD4 genome AF: 0.00102 AC: 155AN: 152274Hom.: 0 Cov.: 32 AF XY: 0.00101 AC XY: 75AN XY: 74452
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:5
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Uncertain significance, no assertion criteria provided | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jul 13, 2012 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden | Nov 03, 2021 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | PTCH1: BS1 - |
not specified Benign:3Other:1
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Jul 21, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Nov 03, 2022 | - - |
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 18, 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:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. - |
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 03, 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. - |
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Feb 11, 2022 | - - |
PTCH1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 24, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Holoprosencephaly 7 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at