rs1060502270
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP3
The NM_000264.5(PTCH1):c.1250A>T(p.Gln417Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. Q417R) has been classified as Uncertain significance.
Frequency
Consequence
NM_000264.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.1250A>T | p.Gln417Leu | missense_variant | 9/24 | ENST00000331920.11 | |
PTCH1 | NM_001083603.3 | c.1247A>T | p.Gln416Leu | missense_variant | 9/24 | ENST00000437951.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.1250A>T | p.Gln417Leu | missense_variant | 9/24 | 5 | NM_000264.5 | A2 | |
PTCH1 | ENST00000437951.6 | c.1247A>T | p.Gln416Leu | missense_variant | 9/24 | 5 | NM_001083603.3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 12, 2022 | The p.Q417L variant (also known as c.1250A>T), located in coding exon 9 of the PTCH1 gene, results from an A to T substitution at nucleotide position 1250. The glutamine at codon 417 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious 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