9-95458026-G-A
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BS1BS2
The NM_000264.5(PTCH1):c.3155C>T(p.Thr1052Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,613,990 control chromosomes in the GnomAD database, including 2 homozygotes. 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. T1052K) has been classified as Uncertain significance.
Frequency
Consequence
NM_000264.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.3155C>T | p.Thr1052Met | missense_variant | 18/24 | ENST00000331920.11 | |
PTCH1 | NM_001083603.3 | c.3152C>T | p.Thr1051Met | missense_variant | 18/24 | ENST00000437951.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.3155C>T | p.Thr1052Met | missense_variant | 18/24 | 5 | NM_000264.5 | A2 | |
PTCH1 | ENST00000437951.6 | c.3152C>T | p.Thr1051Met | missense_variant | 18/24 | 5 | NM_001083603.3 |
Frequencies
GnomAD3 genomes AF: 0.000611 AC: 93AN: 152180Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000649 AC: 163AN: 251056Hom.: 1 AF XY: 0.000648 AC XY: 88AN XY: 135778
GnomAD4 exome AF: 0.00127 AC: 1858AN: 1461810Hom.: 2 Cov.: 32 AF XY: 0.00120 AC XY: 870AN XY: 727196
GnomAD4 genome AF: 0.000611 AC: 93AN: 152180Hom.: 0 Cov.: 33 AF XY: 0.000632 AC XY: 47AN XY: 74344
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:8
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 09, 2021 | This variant is associated with the following publications: (PMID: 26893459, 26353884, 27498913, 22885699, 11941477, 24728327, 26875496, 22703879, 21188540, 24055113, 25637381, 22820256, 23718828, 17001668, 20635334, 24686850, 24211491, 26489027, 26986070, 27153395, 27930734, 29575684, 33209614) - |
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Apr 04, 2021 | - - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2023 | PTCH1: BS1 - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
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 | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Holoprosencephaly 7 Pathogenic:1Uncertain:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 01, 2006 | - - |
Uncertain significance, 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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not specified Uncertain:1Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Aug 15, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 26, 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. - |
Benign, criteria provided, single submitter | curation | Sema4, Sema4 | Dec 04, 2020 | - - |
PTCH1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 17, 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 sequence Benign:1
Likely benign, no assertion criteria provided | research | CSER _CC_NCGL, University of Washington | Jun 01, 2014 | - - |
Gorlin syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at