rs786204193
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2
The NM_000264.5(PTCH1):c.49_51dupGGC(p.Gly17dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000193 in 1,399,428 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000264.5 conservative_inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.49_51dupGGC | p.Gly17dup | conservative_inframe_insertion | Exon 1 of 24 | ENST00000331920.11 | NP_000255.2 | |
PTCH1 | NM_001083603.3 | c.199-1714_199-1712dupGGC | intron_variant | Intron 1 of 23 | ENST00000437951.6 | NP_001077072.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.49_51dupGGC | p.Gly17dup | conservative_inframe_insertion | Exon 1 of 24 | 5 | NM_000264.5 | ENSP00000332353.6 | ||
PTCH1 | ENST00000437951.6 | c.199-1714_199-1712dupGGC | intron_variant | Intron 1 of 23 | 5 | NM_001083603.3 | ENSP00000389744.2 |
Frequencies
GnomAD3 genomes AF: 0.0000398 AC: 6AN: 150744Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000460 AC: 1AN: 21730Hom.: 0 AF XY: 0.0000796 AC XY: 1AN XY: 12556
GnomAD4 exome AF: 0.0000168 AC: 21AN: 1248574Hom.: 0 Cov.: 33 AF XY: 0.00000985 AC XY: 6AN XY: 608970
GnomAD4 genome AF: 0.0000398 AC: 6AN: 150854Hom.: 0 Cov.: 32 AF XY: 0.0000136 AC XY: 1AN XY: 73690
ClinVar
Submissions by phenotype
not provided Uncertain:2
In-frame duplication of 1 amino acid in a repetitive region with no known function; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge -
To the best of our knowledge, this variant has not been reported in the published literature. The frequency of this variant in the general population, 0.000046 (1/21730 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Based on the available information, we are unable to determine the clinical significance of this variant. -
Gorlin syndrome Benign:1
- -
Hereditary cancer-predisposing syndrome Benign:1
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