rs200189314
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP2BP6_Very_StrongBS2
The NM_000264.5(PTCH1):c.2215C>T(p.His739Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000725 in 1,614,058 control chromosomes in the GnomAD database, including 1 homozygotes. 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. H739F) has been classified as Likely benign.
Frequency
Consequence
NM_000264.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.2215C>T | p.His739Tyr | missense_variant | 14/24 | ENST00000331920.11 | |
PTCH1 | NM_001083603.3 | c.2212C>T | p.His738Tyr | missense_variant | 14/24 | ENST00000437951.6 | |
LOC100507346 | NR_038982.1 | n.724G>A | non_coding_transcript_exon_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.2215C>T | p.His739Tyr | missense_variant | 14/24 | 5 | NM_000264.5 | A2 | |
PTCH1 | ENST00000437951.6 | c.2212C>T | p.His738Tyr | missense_variant | 14/24 | 5 | NM_001083603.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000789 AC: 12AN: 152182Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000131 AC: 33AN: 251490Hom.: 0 AF XY: 0.000125 AC XY: 17AN XY: 135918
GnomAD4 exome AF: 0.0000718 AC: 105AN: 1461876Hom.: 1 Cov.: 33 AF XY: 0.0000633 AC XY: 46AN XY: 727236
GnomAD4 genome ? AF: 0.0000789 AC: 12AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74342
ClinVar
Submissions by phenotype
Gorlin syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 10, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 24, 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