rs4880179

chr9-136977596-A-Gchr9-136977596-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000954.6(PTGDS):c.18A>G(p.Thr6=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.963 in 1,601,766 control chromosomes in the GnomAD database, including 743,442 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.95 (68606 hom., cov: 35)
  • Exomes 𝑓: 0.96 (674836 hom.)
• Consequence: PTGDS NM_000954.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.73

Genes affected

PTGDS (HGNC:9592): (prostaglandin D2 synthase) The protein encoded by this gene is a glutathione-independent prostaglandin D synthase that catalyzes the conversion of prostaglandin H2 (PGH2) to postaglandin D2 (PGD2). PGD2 functions as a neuromodulator as well as a trophic factor in the central nervous system. PGD2 is also involved in smooth muscle contraction/relaxation and is a potent inhibitor of platelet aggregation. This gene is preferentially expressed in brain. Studies with transgenic mice overexpressing this gene suggest that this gene may be also involved in the regulation of non-rapid eye movement sleep. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP7: Synonymous conserved (PhyloP=-2.73 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGDS	NM_000954.6	c.18A>G	p.Thr6=	synonymous_variant	1/7	ENST00000371625.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGDS	ENST00000371625.8	c.18A>G	p.Thr6=	synonymous_variant	1/7	1	NM_000954.6	P1
PTGDS	ENST00000457950.5	c.18A>G	p.Thr6=	synonymous_variant	1/5	3
PTGDS	ENST00000640716.1	c.18A>G	p.Thr6=	synonymous_variant	4/5	5
PTGDS	ENST00000371623.5	n.81A>G		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes AF: 0.949 AC: 144402 AN: 152226 Hom.: 68560 Cov.: 35

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.986

Gnomad AMR AF: 0.966

Gnomad ASJ AF: 0.960

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.986

Gnomad FIN AF: 0.966

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.964

Gnomad OTH AF: 0.953

GnomAD3 exomes AF: 0.968 AC: 228790 AN: 236238 Hom.: 110846 AF XY: 0.970 AC XY: 125455 AN XY: 129324

Gnomad AFR exome AF: 0.896

Gnomad AMR exome AF: 0.981

Gnomad ASJ exome AF: 0.966

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.984

Gnomad FIN exome AF: 0.970

Gnomad NFE exome AF: 0.966

Gnomad OTH exome AF: 0.966

GnomAD4 exome AF: 0.965 AC: 1398485 AN: 1449422 Hom.: 674836 Cov.: 43 AF XY: 0.965 AC XY: 696045 AN XY: 720954

Gnomad4 AFR exome AF: 0.896

Gnomad4 AMR exome AF: 0.979

Gnomad4 ASJ exome AF: 0.964

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.984

Gnomad4 FIN exome AF: 0.971

Gnomad4 NFE exome AF: 0.963

Gnomad4 OTH exome AF: 0.965

GnomAD4 genome AF: 0.949 AC: 144507 AN: 152344 Hom.: 68606 Cov.: 35 AF XY: 0.951 AC XY: 70822 AN XY: 74504

Gnomad4 AFR AF: 0.900

Gnomad4 AMR AF: 0.966

Gnomad4 ASJ AF: 0.960

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.986

Gnomad4 FIN AF: 0.966

Gnomad4 NFE AF: 0.964

Gnomad4 OTH AF: 0.953

Alfa AF: 0.959 Hom.: 55506

Bravo AF: 0.947

Asia WGS AF: 0.989 AC: 3437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.79
Dann	Benign	0.59

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: rs4880179; hg19: chr9-139872048; COSMIC: COSV56400996; COSMIC: COSV56400996;