Variant 20-49524089-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PP5_ModerateBP4BS2_Supporting

The NM_000961.4(PTGIS):c.824G>A(p.Arg275Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,614,220 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: 𝑓 0.00095 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 2 hom. )

Consequence

PTGIS
NM_000961.4 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 2.71

Variant links:

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]

PTGIS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PP5

Variant 20-49524089-C-T is Pathogenic according to our data. Variant chr20-49524089-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 208402.Status of the report is criteria_provided_single_submitter, 1 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.027326822). . Strength limited to SUPPORTING due to the PP5.

BS2

High Homozygotes in GnomAdExome4 at 2 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGIS	NM_000961.4 link	c.824G>A	p.Arg275Gln	missense_variant	6/10	ENST00000244043.5	NP_000952.1	Q16647

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGIS	ENST00000244043.5 link	c.824G>A	p.Arg275Gln	missense_variant	6/10	1	NM_000961.4	ENSP00000244043.3		Q16647
PTGIS	ENST00000478971.1 link	n.645G>A		non_coding_transcript_exon_variant	5/9	1

Frequencies

GnomAD3 genomes

AF:

0.000946

AC:

144

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00134

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000979

AC:

246

AN:

251352

Hom.:

AF XY:

0.00100

AC XY:

136

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00107

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00152

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00120

AC:

1758

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00116

AC XY:

847

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.00110

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000220

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.00141

Gnomad4 OTH exome

AF:

0.00119

GnomAD4 genome

AF:

0.000945

AC:

144

AN:

152332

Hom.:

Cov.:

AF XY:

0.000926

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000240

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000376

Gnomad4 NFE

AF:

0.00134

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00125

Hom.:

Bravo

AF:

0.00109

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.000923

AC:

112

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00234

EpiControl

AF:

0.00249

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Childhood-onset schizophrenia

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

Dr. Guy Rouleau's laboratory, McGill University

Jan 01, 2014

COS with Obsessive Compulsive Disorder, Expressive Language Disorder -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.18

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Benign

0.67

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.022

MetaRNN

Benign

0.027

MetaSVM

Benign

-0.56

MutationAssessor

Benign

2.0

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-2.0

REVEL

Benign

0.29

Sift

Benign

0.099

Sift4G

Benign

0.10

Polyphen

1.0

Vest4

0.60

MVP

0.80

MPC

0.34

ClinPred

0.59

GERP RS

5.1

Varity_R

0.37

gMVP

0.58

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over