chr9-136977596-A-G

Variant names:

• chr9-136977596-A-G
• rs4880179
• NM_000954.6:c.18A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000954.6(PTGDS):​c.18A>G​(p.Thr6Thr) 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
• Publications: 18 publications found

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]

ENSG00000284341 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000954.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGDS	NM_000954.6	MANE Select	c.18A>G	p.Thr6Thr	synonymous	Exon 1 of 7	NP_000945.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGDS	ENST00000371625.8	TSL:1 MANE Select	c.18A>G	p.Thr6Thr	synonymous	Exon 1 of 7	ENSP00000360687.3
	ENSG00000284341	ENST00000471521.5	TSL:5	n.18A>G		non_coding_transcript_exon	Exon 1 of 10	ENSP00000435033.1
	PTGDS	ENST00000457950.5	TSL:3	c.18A>G	p.Thr6Thr	synonymous	Exon 1 of 5	ENSP00000392633.1

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

GnomAD2 exomes AF: 0.968 AC: 228790 AN: 236238 AF XY: 0.970

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 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

African (AFR) AF: 0.896 AC: 29372 AN: 32774

American (AMR) AF: 0.979 AC: 41086 AN: 41950

Ashkenazi Jewish (ASJ) AF: 0.964 AC: 24789 AN: 25710

East Asian (EAS) AF: 1.00 AC: 39186 AN: 39190

South Asian (SAS) AF: 0.984 AC: 83703 AN: 85028

European-Finnish (FIN) AF: 0.971 AC: 50252 AN: 51770

Middle Eastern (MID) AF: 0.973 AC: 5563 AN: 5720

European-Non Finnish (NFE) AF: 0.963 AC: 1066871 AN: 1107508

Other (OTH) AF: 0.965 AC: 57663 AN: 59772

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

African (AFR) AF: 0.900 AC: 37399 AN: 41568

American (AMR) AF: 0.966 AC: 14798 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.960 AC: 3332 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5184 AN: 5186

South Asian (SAS) AF: 0.986 AC: 4766 AN: 4834

European-Finnish (FIN) AF: 0.966 AC: 10266 AN: 10630

Middle Eastern (MID) AF: 0.976 AC: 287 AN: 294

European-Non Finnish (NFE) AF: 0.964 AC: 65561 AN: 68022

Other (OTH) AF: 0.953 AC: 2015 AN: 2114

Alfa AF: 0.957 Hom.: 70883

Bravo AF: 0.947

Asia WGS AF: 0.989 AC: 3437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.79
DANN	Benign	0.59
PhyloP100		-2.7
PromoterAI		0.022	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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