rs150373546
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4_ModerateBP6BS2
The NM_000264.5(PTCH1):c.3992C>T(p.Ser1331Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000211 in 1,612,928 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. S1331C) has been classified as Likely benign.
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.3992C>T | p.Ser1331Phe | missense_variant | 23/24 | ENST00000331920.11 | |
PTCH1 | NM_001083603.3 | c.3989C>T | p.Ser1330Phe | missense_variant | 23/24 | ENST00000437951.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.3992C>T | p.Ser1331Phe | missense_variant | 23/24 | 5 | NM_000264.5 | A2 | |
PTCH1 | ENST00000437951.6 | c.3989C>T | p.Ser1330Phe | missense_variant | 23/24 | 5 | NM_001083603.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152244Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000406 AC: 1AN: 246236Hom.: 0 AF XY: 0.00000744 AC XY: 1AN XY: 134420
GnomAD4 exome AF: 0.0000219 AC: 32AN: 1460684Hom.: 0 Cov.: 30 AF XY: 0.0000193 AC XY: 14AN XY: 726640
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152244Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74368
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 22, 2021 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Gorlin syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 10, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 18, 2023 | 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