rs751511116
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 3P and 8B. PP2PP3_ModerateBP6_Very_Strong
The NM_000264.5(PTCH1):c.217C>T(p.Arg73Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,611,946 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 Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R73P) 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 -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.217C>T | p.Arg73Trp | missense_variant | 2/24 | ENST00000331920.11 | |
PTCH1 | NM_001083603.3 | c.214C>T | p.Arg72Trp | missense_variant | 2/24 | ENST00000437951.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.217C>T | p.Arg73Trp | missense_variant | 2/24 | 5 | NM_000264.5 | A2 | |
PTCH1 | ENST00000437951.6 | c.214C>T | p.Arg72Trp | missense_variant | 2/24 | 5 | NM_001083603.3 | ||
ENST00000604104.1 | n.350G>A | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152154Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000161 AC: 4AN: 248528Hom.: 0 AF XY: 0.0000223 AC XY: 3AN XY: 134686
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1459792Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 726204
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152154Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74316
ClinVar
Submissions by phenotype
Gorlin syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 21, 2022 | 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