9-95467215-C-T
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 1P and 13B. PP2BP4BP6_Very_StrongBS2
The NM_000264.5(PTCH1):c.2461G>A(p.Asp821Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000155 in 1,613,930 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 Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D821E) has been classified as Uncertain significance.
Frequency
Consequence
NM_000264.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.2461G>A | p.Asp821Asn | missense_variant | 15/24 | ENST00000331920.11 | |
PTCH1 | NM_001083603.3 | c.2458G>A | p.Asp820Asn | missense_variant | 15/24 | ENST00000437951.6 | |
LOC100507346 | NR_038982.1 | n.476C>T | non_coding_transcript_exon_variant | 2/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.2461G>A | p.Asp821Asn | missense_variant | 15/24 | 5 | NM_000264.5 | A2 | |
PTCH1 | ENST00000437951.6 | c.2458G>A | p.Asp820Asn | missense_variant | 15/24 | 5 | NM_001083603.3 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152068Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251492Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135922
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461862Hom.: 0 Cov.: 33 AF XY: 0.0000138 AC XY: 10AN XY: 727236
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152068Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74240
ClinVar
Submissions by phenotype
Gorlin syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 28, 2024 | This alteration is classified as 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