rs786204193
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2
The NM_000264.5(PTCH1):c.46_51dupGGCGGC(p.Gly16_Gly17dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000715 in 1,399,428 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000064 ( 0 hom. )
Consequence
PTCH1
NM_000264.5 conservative_inframe_insertion
NM_000264.5 conservative_inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.27
Genes affected
PTCH1 (HGNC:9585): (patched 1) This gene encodes a member of the patched family of proteins and a component of the hedgehog signaling pathway. Hedgehog signaling is important in embryonic development and tumorigenesis. The encoded protein is the receptor for the secreted hedgehog ligands, which include sonic hedgehog, indian hedgehog and desert hedgehog. Following binding by one of the hedgehog ligands, the encoded protein is trafficked away from the primary cilium, relieving inhibition of the G-protein-coupled receptor smoothened, which results in activation of downstream signaling. Mutations of this gene have been associated with basal cell nevus syndrome and holoprosencephaly. [provided by RefSeq, Aug 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP6
Variant 9-95508310-T-TGCCGCC is Benign according to our data. Variant chr9-95508310-T-TGCCGCC is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 570794.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=1}.
BS2
High AC in GnomAdExome4 at 8 AD gene.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| PTCH1 | NM_000264.5 | c.46_51dupGGCGGC | p.Gly16_Gly17dup | conservative_inframe_insertion | Exon 1 of 24 | ENST00000331920.11 | NP_000255.2 | |
| PTCH1 | NM_001083603.3 | c.199-1717_199-1712dupGGCGGC | intron_variant | Intron 1 of 23 | ENST00000437951.6 | NP_001077072.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| PTCH1 | ENST00000331920.11 | c.46_51dupGGCGGC | p.Gly16_Gly17dup | conservative_inframe_insertion | Exon 1 of 24 | 5 | NM_000264.5 | ENSP00000332353.6 | ||
| PTCH1 | ENST00000437951.6 | c.199-1717_199-1712dupGGCGGC | intron_variant | Intron 1 of 23 | 5 | NM_001083603.3 | ENSP00000389744.2 |
Frequencies
GnomAD3 genomes 0.0000133 AC: 2AN: 150744Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000641 AC: 8AN: 1248574Hom.: 0 Cov.: 33 AF XY: 0.00000657 AC XY: 4AN XY: 608970
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GnomAD4 genome 0.0000133 AC: 2AN: 150854Hom.: 0 Cov.: 32 AF XY: 0.0000136 AC XY: 1AN XY: 73690
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Gorlin syndrome Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 09, 2024 | This variant, c.46_51dup, results in the insertion of 2 amino acid(s) of the PTCH1 protein (p.Gly16_Gly17dup), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PTCH1-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
not provided Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Jan 25, 2024 | The PTCH1 c.46_51dup (p.Gly16_Gly17dup) variant has not been reported in individuals with PTCH1-related conditions in the published literature. The frequency of this variant in the general population, 0.000013 (2/150744 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Based on the available information, we are unable to determine the clinical significance of this variant. - |
Hereditary cancer-predisposing syndrome Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 25, 2021 | 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
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at