rs200029534
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000264.5(PTCH1):c.3641C>T(p.Thr1214Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00016 in 1,589,366 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign 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. T1214A) has been classified as Uncertain significance.
Frequency
Consequence
NM_000264.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.3641C>T | p.Thr1214Met | missense_variant | Exon 22 of 24 | 5 | NM_000264.5 | ENSP00000332353.6 | ||
PTCH1 | ENST00000437951.6 | c.3638C>T | p.Thr1213Met | missense_variant | Exon 22 of 24 | 5 | NM_001083603.3 | ENSP00000389744.2 |
Frequencies
GnomAD3 genomes AF: 0.000171 AC: 26AN: 152284Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000359 AC: 73AN: 203394Hom.: 0 AF XY: 0.000522 AC XY: 57AN XY: 109274
GnomAD4 exome AF: 0.000159 AC: 229AN: 1436964Hom.: 2 Cov.: 31 AF XY: 0.000250 AC XY: 178AN XY: 712458
GnomAD4 genome AF: 0.000171 AC: 26AN: 152402Hom.: 0 Cov.: 33 AF XY: 0.000215 AC XY: 16AN XY: 74534
ClinVar
Submissions by phenotype
Gorlin syndrome Benign:2
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Hereditary cancer-predisposing syndrome Benign:2
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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. -
Fraser syndrome 3 Uncertain:1
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not specified Benign:1
Classification criteria: BP4_moderate -
PTCH1-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at