9-95453599-C-G
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PP2PP3_ModerateBS2
The NM_000264.5(PTCH1):āc.3328G>Cā(p.Asp1110His) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,461,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D1110N) has been classified as Uncertain significance.
Frequency
Consequence
NM_000264.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.3328G>C | p.Asp1110His | missense_variant | 20/24 | ENST00000331920.11 | |
PTCH1 | NM_001083603.3 | c.3325G>C | p.Asp1109His | missense_variant | 20/24 | ENST00000437951.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.3328G>C | p.Asp1110His | missense_variant | 20/24 | 5 | NM_000264.5 | A2 | |
PTCH1 | ENST00000437951.6 | c.3325G>C | p.Asp1109His | missense_variant | 20/24 | 5 | NM_001083603.3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461546Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727092
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Gorlin syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 13, 2021 | This sequence change replaces aspartic acid with histidine at codon 1110 of the PTCH1 protein (p.Asp1110His). The aspartic acid residue is moderately conserved and there is a moderate physicochemical difference between aspartic acid and histidine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with PTCH1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 01, 2019 | The p.D1110H variant (also known as c.3328G>C), located in coding exon 20 of the PTCH1 gene, results from a G to C substitution at nucleotide position 3328. The aspartic acid at codon 1110 is replaced by histidine, an amino acid with similar 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at