9-95478060-G-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM1BP4_ModerateBP6BS2
The NM_000264.5(PTCH1):c.1342C>A(p.Leu448Ile) 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 1,614,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
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
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.1342C>A | p.Leu448Ile | missense_variant | Exon 9 of 24 | 5 | NM_000264.5 | ENSP00000332353.6 | ||
PTCH1 | ENST00000437951.6 | c.1339C>A | p.Leu447Ile | missense_variant | Exon 9 of 24 | 5 | NM_001083603.3 | ENSP00000389744.2 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152218Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251474Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135910
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461882Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727242
GnomAD4 genome AF: 0.0000656 AC: 10AN: 152336Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74494
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
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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. -
Gorlin syndrome Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at