rs201246004
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_000264.5(PTCH1):c.1404C>T(p.Ala468=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,614,176 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000036 ( 0 hom. )
Consequence
PTCH1
NM_000264.5 synonymous
NM_000264.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.16
Genes affected
PTCH1 (HGNC:9585): (patched 1) This gene encodes a member of the patched family of proteins and a component of the hedgehog signaling pathway. Hedgehog signaling is important in embryonic development and tumorigenesis. The encoded protein is the receptor for the secreted hedgehog ligands, which include sonic hedgehog, indian hedgehog and desert hedgehog. Following binding by one of the hedgehog ligands, the encoded protein is trafficked away from the primary cilium, relieving inhibition of the G-protein-coupled receptor smoothened, which results in activation of downstream signaling. Mutations of this gene have been associated with basal cell nevus syndrome and holoprosencephaly. [provided by RefSeq, Aug 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.25).
BP6
?
Variant 9-95477646-G-A is Benign according to our data. Variant chr9-95477646-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 237454.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.16 with no splicing effect.
BS2
?
High AC in GnomAd4 at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.1404C>T | p.Ala468= | synonymous_variant | 10/24 | ENST00000331920.11 | |
PTCH1 | NM_001083603.3 | c.1401C>T | p.Ala467= | synonymous_variant | 10/24 | ENST00000437951.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.1404C>T | p.Ala468= | synonymous_variant | 10/24 | 5 | NM_000264.5 | A2 | |
PTCH1 | ENST00000437951.6 | c.1401C>T | p.Ala467= | synonymous_variant | 10/24 | 5 | NM_001083603.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152178Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251280Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135824
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GnomAD4 exome AF: 0.0000356 AC: 52AN: 1461880Hom.: 0 Cov.: 32 AF XY: 0.0000330 AC XY: 24AN XY: 727242
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152296Hom.: 0 Cov.: 33 AF XY: 0.0000671 AC XY: 5AN XY: 74468
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Gorlin syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 07, 2017 | 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
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at