9-122381691-AAT-TCA

Variant names:

• chr9-122381691-AAT-TCA
• NM_000962.4:c.706_708delAATinsTCA
• PTGS1 p.Asn236Ser

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000962.4(PTGS1):​c.706_708delAATinsTCA​(p.Asn236Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PTGS1 NM_000962.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.97
• Publications: 0 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 12

  Inheritance: SD, AD, AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.706_708delAATinsTCA	p.Asn236Ser	missense	N/A	NP_000953.2
	PTGS1	NM_080591.3		c.706_708delAATinsTCA	p.Asn236Ser	missense	N/A	NP_542158.1	P23219-2
	PTGS1	NM_001271164.2		c.562_564delAATinsTCA	p.Asn188Ser	missense	N/A	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.706_708delAATinsTCA	p.Asn236Ser	missense	N/A	ENSP00000354612.2	P23219-1
	PTGS1	ENST00000223423.8	TSL:1	c.706_708delAATinsTCA	p.Asn236Ser	missense	N/A	ENSP00000223423.4	P23219-2
	PTGS1	ENST00000863393.1		c.760_762delAATinsTCA	p.Asn254Ser	missense	N/A	ENSP00000533452.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr9-125143970;