9-122371212-TTCCTGC-TTCCTGCTCCTGC
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP3
The NM_000962.4(PTGS1):c.44_49dupTGCTCC(p.Leu15_Leu16dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,456,150 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
PTGS1
NM_000962.4 disruptive_inframe_insertion
NM_000962.4 disruptive_inframe_insertion
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 3.31
Publications
4 publications found
Genes affected
PTGS1 (HGNC:9604): (prostaglandin-endoperoxide synthase 1) This is one of two genes encoding similar enzymes that catalyze the conversion of arachidonate to prostaglandin. The encoded protein regulates angiogenesis in endothelial cells, and is inhibited by nonsteroidal anti-inflammatory drugs such as aspirin. Based on its ability to function as both a cyclooxygenase and as a peroxidase, the encoded protein has been identified as a moonlighting protein. The protein may promote cell proliferation during tumor progression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2021]
PTGS1 Gene-Disease associations (from GenCC):
- platelet-type bleeding disorder 12Inheritance: AR, AD, SD Classification: LIMITED Submitted by: ClinGen
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP3
Nonframeshift variant in repetitive region in NM_000962.4
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000962.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PTGS1 | NM_000962.4 | MANE Select | c.44_49dupTGCTCC | p.Leu15_Leu16dup | disruptive_inframe_insertion | Exon 2 of 11 | NP_000953.2 | ||
| PTGS1 | NM_080591.3 | c.44_49dupTGCTCC | p.Leu15_Leu16dup | disruptive_inframe_insertion | Exon 2 of 11 | NP_542158.1 | P23219-2 | ||
| PTGS1 | NM_001271164.2 | c.44_49dupTGCTCC | p.Leu15_Leu16dup | disruptive_inframe_insertion | Exon 2 of 10 | NP_001258093.1 | A0A087X296 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PTGS1 | ENST00000362012.7 | TSL:1 MANE Select | c.44_49dupTGCTCC | p.Leu15_Leu16dup | disruptive_inframe_insertion | Exon 2 of 11 | ENSP00000354612.2 | P23219-1 | |
| PTGS1 | ENST00000223423.8 | TSL:1 | c.44_49dupTGCTCC | p.Leu15_Leu16dup | disruptive_inframe_insertion | Exon 2 of 11 | ENSP00000223423.4 | P23219-2 | |
| PTGS1 | ENST00000863393.1 | c.44_49dupTGCTCC | p.Leu15_Leu16dup | disruptive_inframe_insertion | Exon 2 of 12 | ENSP00000533452.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.00000405 AC: 1AN: 246998 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
246998
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
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Gnomad FIN exome
AF:
Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000343 AC: 5AN: 1456150Hom.: 0 Cov.: 38 AF XY: 0.00000414 AC XY: 3AN XY: 724644 show subpopulations
GnomAD4 exome
AF:
AC:
5
AN:
1456150
Hom.:
Cov.:
38
AF XY:
AC XY:
3
AN XY:
724644
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33472
American (AMR)
AF:
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26128
East Asian (EAS)
AF:
AC:
0
AN:
39694
South Asian (SAS)
AF:
AC:
0
AN:
86254
European-Finnish (FIN)
AF:
AC:
0
AN:
47922
Middle Eastern (MID)
AF:
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
AC:
5
AN:
1111844
Other (OTH)
AF:
AC:
0
AN:
60352
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
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Allele balance
Age Distribution
Exome Het
Variant carriers
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GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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