rs376084632
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 3P and 7B. PM1PP2BP4_ModerateBP6BS2
The NM_000264.5(PTCH1):c.2794G>A(p.Val932Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,614,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. V932V) has been classified as Likely benign.
Frequency
Consequence
NM_000264.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.2794G>A | p.Val932Ile | missense_variant | 17/24 | ENST00000331920.11 | |
PTCH1 | NM_001083603.3 | c.2791G>A | p.Val931Ile | missense_variant | 17/24 | ENST00000437951.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.2794G>A | p.Val932Ile | missense_variant | 17/24 | 5 | NM_000264.5 | A2 | |
PTCH1 | ENST00000437951.6 | c.2791G>A | p.Val931Ile | missense_variant | 17/24 | 5 | NM_001083603.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152178Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251484Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135920
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461878Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727240
GnomAD4 genome ? AF: 0.0000722 AC: 11AN: 152296Hom.: 0 Cov.: 33 AF XY: 0.0000671 AC XY: 5AN XY: 74476
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 18, 2024 | The p.V932I variant (also known as c.2794G>A), located in coding exon 17 of the PTCH1 gene, results from a G to A substitution at nucleotide position 2794. The valine at codon 932 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. - |
Gorlin syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at