rs372555269
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4BP6
The NM_000264.5(PTCH1):c.1903G>T(p.Asp635Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,826 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D635N) has been classified as Likely benign.
Frequency
Consequence
NM_000264.5 missense
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.1903G>T | p.Asp635Tyr | missense_variant | 14/24 | ENST00000331920.11 | |
PTCH1 | NM_001083603.3 | c.1900G>T | p.Asp634Tyr | missense_variant | 14/24 | ENST00000437951.6 | |
LOC100507346 | NR_038982.1 | n.1036C>A | non_coding_transcript_exon_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.1903G>T | p.Asp635Tyr | missense_variant | 14/24 | 5 | NM_000264.5 | A2 | |
PTCH1 | ENST00000437951.6 | c.1900G>T | p.Asp634Tyr | missense_variant | 14/24 | 5 | NM_001083603.3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152036Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251232Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135800
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461790Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 727194
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152036Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74242
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 15, 2023 | The p.D635Y variant (also known as c.1903G>T), located in coding exon 14 of the PTCH1 gene, results from a G to T substitution at nucleotide position 1903. The aspartic acid at codon 635 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Gorlin syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 09, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at