rs1554689404
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_000264.5(PTCH1):c.3643C>T(p.His1215Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,438,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H1215N) has been classified as Likely benign.
Frequency
Consequence
NM_000264.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.3643C>T | p.His1215Tyr | missense_variant | 22/24 | ENST00000331920.11 | |
PTCH1 | NM_001083603.3 | c.3640C>T | p.His1214Tyr | missense_variant | 22/24 | ENST00000437951.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.3643C>T | p.His1215Tyr | missense_variant | 22/24 | 5 | NM_000264.5 | A2 | |
PTCH1 | ENST00000437951.6 | c.3640C>T | p.His1214Tyr | missense_variant | 22/24 | 5 | NM_001083603.3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 6.95e-7 AC: 1AN: 1438846Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1AN XY: 713556
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 19, 2022 | The p.H1215Y variant (also known as c.3643C>T), located in coding exon 22 of the PTCH1 gene, results from a C to T substitution at nucleotide position 3643. The histidine at codon 1215 is replaced by tyrosine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.