20-49513150-C-G

Position:

• chr20-49513150-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000961.4(PTGIS):​c.1136G>C​(p.Arg379Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R379S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTGIS NM_000961.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.74

Genes affected

PTGIS (HGNC:9603): (prostaglandin I2 synthase) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. However, this protein is considered a member of the cytochrome P450 superfamily on the basis of sequence similarity rather than functional similarity. This endoplasmic reticulum membrane protein catalyzes the conversion of prostglandin H2 to prostacyclin (prostaglandin I2), a potent vasodilator and inhibitor of platelet aggregation. An imbalance of prostacyclin and its physiological antagonist thromboxane A2 contribute to the development of myocardial infarction, stroke, and atherosclerosis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGIS	NM_000961.4	c.1136G>C	p.Arg379Pro	missense_variant	8/10	ENST00000244043.5	NP_000952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGIS	ENST00000244043.5	c.1136G>C	p.Arg379Pro	missense_variant	8/10	1	NM_000961.4	ENSP00000244043.3
PTGIS	ENST00000478971.1	n.957G>C		non_coding_transcript_exon_variant	7/9	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 24, 2024

The c.1136G>C (p.R379P) alteration is located in exon 8 (coding exon 8) of the PTGIS gene. This alteration results from a G to C substitution at nucleotide position 1136, causing the arginine (R) at amino acid position 379 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.52	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	2.0	M
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.15
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.52
MutPred		0.56		Loss of sheet (P = 0.0126);
MVP		0.62
MPC		0.44
ClinPred		0.97	D
GERP RS		2.5
Varity_R		0.85
gMVP		0.88

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-48129687;