rs3842795

chr9-122381673-G-Achr9-122381673-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000962.4(PTGS1):c.688G>A(p.Gly230Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000399 in 1,614,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0021 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: PTGS1 NM_000962.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.38

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.01051411).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGS1	NM_000962.4	c.688G>A	p.Gly230Ser	missense_variant	7/11	ENST00000362012.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGS1	ENST00000362012.7	c.688G>A	p.Gly230Ser	missense_variant	7/11	1	NM_000962.4	P1

Frequencies

GnomAD3 genomes AF: 0.00206 AC: 313 AN: 152186 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00729

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.000617 AC: 155 AN: 251396 Hom.: 0 AF XY: 0.000405 AC XY: 55 AN XY: 135872

Gnomad AFR exome AF: 0.00880

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000226 AC: 331 AN: 1461856 Hom.: 0 Cov.: 33 AF XY: 0.000198 AC XY: 144 AN XY: 727232

Gnomad4 AFR exome AF: 0.00860

Gnomad4 AMR exome AF: 0.000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000719

Gnomad4 OTH exome AF: 0.000298

GnomAD4 genome AF: 0.00206 AC: 313 AN: 152304 Hom.: 0 Cov.: 33 AF XY: 0.00187 AC XY: 139 AN XY: 74470

Gnomad4 AFR AF: 0.00727

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.000948

Alfa AF: 0.000246 Hom.: 0

Bravo AF: 0.00227

ESP6500AA AF: 0.00726 AC: 32

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000782 AC: 95

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	22
Dann	Benign	0.60
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.91	D;D;.;D;D;D;D;D
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.011	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.70	T
Polyphen		0.10, 0.025	.;.;B;B;.;.;B;.
Vest4		0.31, 0.29, 0.31, 0.29
MVP		0.69
MPC		0.59
ClinPred		0.032	T
GERP RS		4.8
Varity_R		0.29
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3842795; hg19: chr9-125143952; COSMIC: COSV56291136;