9-95447208-G-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6BP7
The NM_000264.5(PTCH1):c.4048C>A(p.Arg1350=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,632 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. R1350R) has been classified as Likely benign.
Frequency
Consequence
NM_000264.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.4048C>A | p.Arg1350= | synonymous_variant | 23/24 | ENST00000331920.11 | |
PTCH1 | NM_001083603.3 | c.4045C>A | p.Arg1349= | synonymous_variant | 23/24 | ENST00000437951.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.4048C>A | p.Arg1350= | synonymous_variant | 23/24 | 5 | NM_000264.5 | A2 | |
PTCH1 | ENST00000437951.6 | c.4045C>A | p.Arg1349= | synonymous_variant | 23/24 | 5 | NM_001083603.3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000406 AC: 1AN: 246496Hom.: 0 AF XY: 0.00000744 AC XY: 1AN XY: 134360
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460632Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 726614
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Gorlin syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 12, 2021 | This variant has not been reported in the literature in individuals affected with PTCH1-related conditions. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant is not present in population databases (ExAC no frequency). This sequence change affects codon 1350 of the PTCH1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the PTCH1 protein. - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 21, 2023 | 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