19-46623616-C-T

Variant names:

• chr19-46623616-C-T
• rs200973220
• NM_000960.4:c.610G>A

Variant summary

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

The NM_000960.4(PTGIR):​c.610G>A​(p.Gly204Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000449 in 1,549,754 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00045 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00045 (1 hom.)
• Consequence: PTGIR NM_000960.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.46

Genes affected

PTGIR (HGNC:9602): (prostaglandin I2 receptor) The protein encoded by this gene is a member of the G-protein coupled receptor family 1 and has been shown to be a receptor for prostacyclin. Prostacyclin, the major product of cyclooxygenase in macrovascular endothelium, elicits a potent vasodilation and inhibition of platelet aggregation through binding to this receptor. [provided by RefSeq, Jul 2008]

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=0.023366123).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGIR	NM_000960.4	c.610G>A	p.Gly204Ser	missense_variant	Exon 2 of 3	ENST00000291294.7	NP_000951.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGIR	ENST00000291294.7	c.610G>A	p.Gly204Ser	missense_variant	Exon 2 of 3	1	NM_000960.4	ENSP00000291294.1

Frequencies

GnomAD3 genomes AF: 0.000447 AC: 68 AN: 152258 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000981

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000338 AC: 50 AN: 148078 Hom.: 0 AF XY: 0.000315 AC XY: 25 AN XY: 79340

Gnomad AFR exome AF: 0.000252

Gnomad AMR exome AF: 0.000202

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000132

Gnomad FIN exome AF: 0.00167

Gnomad NFE exome AF: 0.000248

Gnomad OTH exome AF: 0.00116

GnomAD4 exome AF: 0.000449 AC: 628 AN: 1397378 Hom.: 1 Cov.: 31 AF XY: 0.000441 AC XY: 304 AN XY: 689638

Gnomad4 AFR exome AF: 0.0000630

Gnomad4 AMR exome AF: 0.000335

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000756

Gnomad4 FIN exome AF: 0.00222

Gnomad4 NFE exome AF: 0.000441

Gnomad4 OTH exome AF: 0.000500

GnomAD4 genome AF: 0.000446 AC: 68 AN: 152376 Hom.: 0 Cov.: 33 AF XY: 0.000470 AC XY: 35 AN XY: 74520

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.000980

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00207

Gnomad4 NFE AF: 0.000382

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000331 Hom.: 0

Bravo AF: 0.000400

ESP6500AA AF: 0.000241 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000236 AC: 25

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.610G>A (p.G204S) alteration is located in exon 2 (coding exon 1) of the PTGIR gene. This alteration results from a G to A substitution at nucleotide position 610, causing the glycine (G) at amino acid position 204 to be replaced by a serine (S). 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	0.14
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T;.
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.64	T;T
M_CAP	Benign	0.081	D
MetaRNN	Benign	0.023	T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.50	N;.
REVEL	Benign	0.086
Sift	Benign	0.44	T;.
Sift4G	Benign	0.44	T;T
Polyphen		0.13	B;.
Vest4		0.15
MVP		0.85
MPC		0.18
ClinPred		0.015	T
GERP RS		3.7
Varity_R		0.14
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs200973220; hg19: chr19-47126873;