chr9-95449086-C-T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2BP4_ModerateBP6_Very_StrongBS2
The NM_000264.5(PTCH1):c.3787G>A(p.Val1263Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000142 in 1,614,116 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 Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1263A) has been classified as Uncertain significance.
Frequency
Consequence
NM_000264.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.3787G>A | p.Val1263Ile | missense_variant | 22/24 | ENST00000331920.11 | |
PTCH1 | NM_001083603.3 | c.3784G>A | p.Val1262Ile | missense_variant | 22/24 | ENST00000437951.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.3787G>A | p.Val1263Ile | missense_variant | 22/24 | 5 | NM_000264.5 | A2 | |
PTCH1 | ENST00000437951.6 | c.3784G>A | p.Val1262Ile | missense_variant | 22/24 | 5 | NM_001083603.3 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152242Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000799 AC: 2AN: 250400Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135448
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461874Hom.: 0 Cov.: 31 AF XY: 0.0000179 AC XY: 13AN XY: 727242
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152242Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74372
ClinVar
Submissions by phenotype
Gorlin syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 13, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 24, 2024 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at