rs149691476
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_000264.5(PTCH1):c.3624C>T(p.Ala1208=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000092 in 1,575,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A1208A) has been classified as Likely benign.
Frequency
Consequence
NM_000264.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.3624C>T | p.Ala1208= | synonymous_variant | 22/24 | ENST00000331920.11 | |
PTCH1 | NM_001083603.3 | c.3621C>T | p.Ala1207= | synonymous_variant | 22/24 | ENST00000437951.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.3624C>T | p.Ala1208= | synonymous_variant | 22/24 | 5 | NM_000264.5 | A2 | |
PTCH1 | ENST00000437951.6 | c.3621C>T | p.Ala1207= | synonymous_variant | 22/24 | 5 | NM_001083603.3 |
Frequencies
GnomAD3 genomes ? AF: 0.000552 AC: 84AN: 152282Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000142 AC: 26AN: 183546Hom.: 0 AF XY: 0.000123 AC XY: 12AN XY: 97896
GnomAD4 exome AF: 0.0000429 AC: 61AN: 1423210Hom.: 0 Cov.: 31 AF XY: 0.0000270 AC XY: 19AN XY: 704244
GnomAD4 genome ? AF: 0.000551 AC: 84AN: 152400Hom.: 0 Cov.: 33 AF XY: 0.000617 AC XY: 46AN XY: 74528
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Mar 16, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 12, 2018 | - - |
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 17, 2017 | 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 | Jun 16, 2021 | - - |
PTCH1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 26, 2019 | 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). - |
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