rs1208489068
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_000264.5(PTCH1):c.2704-3T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,614,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000264.5 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.2704-3T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000331920.11 | |||
PTCH1 | NM_001083603.3 | c.2701-3T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000437951.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.2704-3T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_000264.5 | A2 | |||
PTCH1 | ENST00000437951.6 | c.2701-3T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_001083603.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152236Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251306Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135844
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461746Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8AN XY: 727194
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152354Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74504
ClinVar
Submissions by phenotype
Gorlin syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 10, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. This sequence change falls in intron 16 of the PTCH1 gene. It does not directly change the encoded amino acid sequence of the PTCH1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (no rsID available, gnomAD 0.02%). This variant has been observed in individual(s) with nevoid basal cell carcinoma (NBCC) syndrome (PMID: 19002359). This variant is also known as IVS16-3T>C. ClinVar contains an entry for this variant (Variation ID: 524536). - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 15, 2021 | The c.2704-3T>C intronic variant results from a T to C substitution 3 nucleotides upstream from coding exon 17 in the PTCH1 gene. This alteration was previously identified in an individual with nevoid basal cell carcinoma syndrome (NBCCS) in conjunction with a pathogenic frameshift mutation; however, the phase of these two alterations (cis or trans) was not determined (Abe S et al. Acta Derm. Venereol., 2008;88:635-6). Of note, this alteration is also designated IVS16-3T>C in the published literature. This nucleotide position is poorly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at