NM_000963.4:c.720T>C

Variant names:

• chr1-186676836-A-G
• rs1181816669
• NM_000963.4:c.720T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000963.4(PTGS2):​c.720T>C​(p.Tyr240Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000549 in 1,457,756 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: PTGS2 NM_000963.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.651
• Publications: 0 publications found

Genes affected

PTGS2 (HGNC:9605): (prostaglandin-endoperoxide synthase 2) Prostaglandin-endoperoxide synthase (PTGS), also known as cyclooxygenase, is the key enzyme in prostaglandin biosynthesis, and acts both as a dioxygenase and as a peroxidase. There are two isozymes of PTGS: a constitutive PTGS1 and an inducible PTGS2, which differ in their regulation of expression and tissue distribution. This gene encodes the inducible isozyme. It is regulated by specific stimulatory events, suggesting that it is responsible for the prostanoid biosynthesis involved in inflammation and mitogenesis. [provided by RefSeq, Feb 2009]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 1-186676836-A-G is Benign according to our data. Variant chr1-186676836-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 765337.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000963.4. 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
	PTGS2	NM_000963.4	MANE Select	c.720T>C	p.Tyr240Tyr	synonymous	Exon 6 of 10	NP_000954.1	P35354

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGS2	ENST00000367468.10	TSL:1 MANE Select	c.720T>C	p.Tyr240Tyr	synonymous	Exon 6 of 10	ENSP00000356438.5	P35354
	PTGS2	ENST00000490885.6	TSL:1	n.853T>C		non_coding_transcript_exon	Exon 6 of 9
	PTGS2	ENST00000559627.1	TSL:1	n.*118T>C		non_coding_transcript_exon	Exon 6 of 10	ENSP00000454130.1	Q6ZYK7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000200 AC: 5 AN: 250498 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000165

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.00000549 AC: 8 AN: 1457756 Hom.: 0 Cov.: 31 AF XY: 0.00000414 AC XY: 3 AN XY: 724950

African (AFR) AF: 0.00 AC: 0 AN: 33410

American (AMR) AF: 0.00 AC: 0 AN: 44576

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26084

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39550

South Asian (SAS) AF: 0.00 AC: 0 AN: 85106

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53268

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5144

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1110440

Other (OTH) AF: 0.00 AC: 0 AN: 60178

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	1.3
DANN	Benign	0.43
PhyloP100		0.65
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1181816669; hg19: chr1-186645968;