chr9-95447312-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM5PP2BP6
The NM_000264.5(PTCH1):c.3944C>G(p.Pro1315Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,612,906 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P1315H) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.3944C>G | p.Pro1315Arg | missense_variant | 23/24 | ENST00000331920.11 | |
PTCH1 | NM_001083603.3 | c.3941C>G | p.Pro1314Arg | missense_variant | 23/24 | ENST00000437951.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.3944C>G | p.Pro1315Arg | missense_variant | 23/24 | 5 | NM_000264.5 | A2 | |
PTCH1 | ENST00000437951.6 | c.3941C>G | p.Pro1314Arg | missense_variant | 23/24 | 5 | NM_001083603.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 151992Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000122 AC: 3AN: 246178Hom.: 0 AF XY: 0.00000744 AC XY: 1AN XY: 134464
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1460914Hom.: 0 Cov.: 70 AF XY: 0.00000550 AC XY: 4AN XY: 726768
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 151992Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74216
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 31, 2023 | The p.P1315R variant (also known as c.3944C>G), located in coding exon 23 of the PTCH1 gene, results from a C to G substitution at nucleotide position 3944. The proline at codon 1315 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. 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. - |
Gorlin syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Oct 22, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at