rs536440590
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2BP4_StrongBP6_Very_StrongBS2
The NM_000264.5(PTCH1):c.3953C>T(p.Pro1318Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000862 in 1,613,162 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 Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1318R) 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 -15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.3953C>T | p.Pro1318Leu | missense_variant | 23/24 | ENST00000331920.11 | |
PTCH1 | NM_001083603.3 | c.3950C>T | p.Pro1317Leu | missense_variant | 23/24 | ENST00000437951.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.3953C>T | p.Pro1318Leu | missense_variant | 23/24 | 5 | NM_000264.5 | A2 | |
PTCH1 | ENST00000437951.6 | c.3950C>T | p.Pro1317Leu | missense_variant | 23/24 | 5 | NM_001083603.3 |
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 152198Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000195 AC: 48AN: 246130Hom.: 0 AF XY: 0.000253 AC XY: 34AN XY: 134454
GnomAD4 exome AF: 0.0000835 AC: 122AN: 1460846Hom.: 0 Cov.: 30 AF XY: 0.000106 AC XY: 77AN XY: 726730
GnomAD4 genome AF: 0.000112 AC: 17AN: 152316Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10AN XY: 74476
ClinVar
Submissions by phenotype
Gorlin syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Oral and Maxillofacial Surgery, Tokyo Medical and Dental University | - | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | May 07, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 04, 2021 | This alteration is classified as 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