9-95478184-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP6
The NM_000264.5(PTCH1):c.1218G>A(p.Val406=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,880 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). Synonymous variant affecting the same amino acid position (i.e. V406V) has been classified as Likely benign.
Frequency
Consequence
NM_000264.5 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.1218G>A | p.Val406= | splice_region_variant, synonymous_variant | 9/24 | ENST00000331920.11 | |
PTCH1 | NM_001083603.3 | c.1215G>A | p.Val405= | splice_region_variant, synonymous_variant | 9/24 | ENST00000437951.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.1218G>A | p.Val406= | splice_region_variant, synonymous_variant | 9/24 | 5 | NM_000264.5 | A2 | |
PTCH1 | ENST00000437951.6 | c.1215G>A | p.Val405= | splice_region_variant, synonymous_variant | 9/24 | 5 | NM_001083603.3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251490Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135918
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461880Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727242
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Jul 20, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 14, 2019 | 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 31, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown. - |
Gorlin syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at