rs1354741081
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_000264.5(PTCH1):c.27G>T(p.Glu9Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000067 in 149,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E9K) has been classified as Uncertain significance.
Frequency
Consequence
NM_000264.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.27G>T | p.Glu9Asp | missense_variant | 1/24 | ENST00000331920.11 | |
PTCH1 | NM_001083603.3 | c.199-1736G>T | intron_variant | ENST00000437951.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.27G>T | p.Glu9Asp | missense_variant | 1/24 | 5 | NM_000264.5 | A2 | |
PTCH1 | ENST00000437951.6 | c.199-1736G>T | intron_variant | 5 | NM_001083603.3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000670 AC: 1AN: 149310Hom.: 0 Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1123250Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 539720
GnomAD4 genome ? AF: 0.00000670 AC: 1AN: 149310Hom.: 0 Cov.: 32 AF XY: 0.0000137 AC XY: 1AN XY: 72856
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 27, 2022 | The p.E9D variant (also known as c.27G>T), located in coding exon 1 of the PTCH1 gene, results from a G to T substitution at nucleotide position 27. The glutamic acid at codon 9 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated 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