rs751374954
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_000264.5(PTCH1):c.3168+34A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000545 in 1,613,380 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 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000057 ( 0 hom. )
Consequence
PTCH1
NM_000264.5 intron
NM_000264.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.15
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 -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
?
Variant 9-95457979-T-C is Benign according to our data. Variant chr9-95457979-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 255682.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.3168+34A>G | intron_variant | ENST00000331920.11 | |||
PTCH1 | NM_001083603.3 | c.3165+34A>G | intron_variant | ENST00000437951.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.3168+34A>G | intron_variant | 5 | NM_000264.5 | A2 | |||
PTCH1 | ENST00000437951.6 | c.3165+34A>G | intron_variant | 5 | NM_001083603.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152202Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000240 AC: 60AN: 249596Hom.: 0 AF XY: 0.000207 AC XY: 28AN XY: 135210
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GnomAD4 exome AF: 0.0000568 AC: 83AN: 1461178Hom.: 0 Cov.: 31 AF XY: 0.0000605 AC XY: 44AN XY: 726898
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152202Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74362
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at