9-95461924-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PP2PP3BP6BS2
The NM_000264.5(PTCH1):c.2635G>A(p.Asp879Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000206 in 1,614,104 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic 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. D879D) 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 -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.2635G>A | p.Asp879Asn | missense_variant | 16/24 | ENST00000331920.11 | |
PTCH1 | NM_001083603.3 | c.2632G>A | p.Asp878Asn | missense_variant | 16/24 | ENST00000437951.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.2635G>A | p.Asp879Asn | missense_variant | 16/24 | 5 | NM_000264.5 | A2 | |
PTCH1 | ENST00000437951.6 | c.2632G>A | p.Asp878Asn | missense_variant | 16/24 | 5 | NM_001083603.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152212Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251490Hom.: 0 AF XY: 0.0000883 AC XY: 12AN XY: 135920
GnomAD4 exome AF: 0.000223 AC: 326AN: 1461892Hom.: 1 Cov.: 32 AF XY: 0.000184 AC XY: 134AN XY: 727248
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74354
ClinVar
Submissions by phenotype
Gorlin syndrome Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | St. Jude Molecular Pathology, St. Jude Children's Research Hospital | Feb 11, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 11, 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. - |
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Sep 01, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Dec 15, 2022 | To the best of our knowledge, the variant has not been reported in the published literature. The frequency of this variant in the general population, 0.0001 (13/129200 chromosomes in European (Non-Finnish) subpopulation, http://gnomad.broadinstitute.org), is higher than would generally be expected for pathogenic variants in this gene. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is deleterious or benign. Based on the available information, we are unable to determine the clinical significance of this variant. - |
Gorlin syndrome;C1835820:Holoprosencephaly 7;C2751544:Basal cell carcinoma, susceptibility to, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at