9-95447223-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 3P and 3B. PM2PP2BP4_ModerateBP6
The NM_000264.5(PTCH1):c.4033C>G(p.Arg1345Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,611,580 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1345C) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.4033C>G | p.Arg1345Gly | missense_variant | 23/24 | ENST00000331920.11 | |
PTCH1 | NM_001083603.3 | c.4030C>G | p.Arg1344Gly | missense_variant | 23/24 | ENST00000437951.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.4033C>G | p.Arg1345Gly | missense_variant | 23/24 | 5 | NM_000264.5 | A2 | |
PTCH1 | ENST00000437951.6 | c.4030C>G | p.Arg1344Gly | missense_variant | 23/24 | 5 | NM_001083603.3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152194Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000813 AC: 2AN: 246054Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134292
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1459268Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 725992
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152312Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74486
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 24, 2022 | The c.4033C>G (p.R1345G) alteration is located in exon 23 (coding exon 23) of the PTCH1 gene. This alteration results from a C to G substitution at nucleotide position 4033, causing the arginine (R) at amino acid position 1345 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Gorlin syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 13, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at