rs776424978
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4BP6
The NM_000264.5(PTCH1):c.361C>T(p.Leu121Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,434 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L121V) 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.361C>T | p.Leu121Phe | missense_variant | 2/24 | ENST00000331920.11 | |
PTCH1 | NM_001083603.3 | c.358C>T | p.Leu120Phe | missense_variant | 2/24 | ENST00000437951.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.361C>T | p.Leu121Phe | missense_variant | 2/24 | 5 | NM_000264.5 | A2 | |
PTCH1 | ENST00000437951.6 | c.358C>T | p.Leu120Phe | missense_variant | 2/24 | 5 | NM_001083603.3 | ||
ENST00000604104.1 | n.206G>A | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 249998Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135362
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460434Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726502
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 25, 2024 | The p.L121F variant (also known as c.361C>T), located in coding exon 2 of the PTCH1 gene, results from a C to T substitution at nucleotide position 361. The leucine at codon 121 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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 | Dec 06, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at