chr9-136977596-A-G

Variant names:

• chr9-136977596-A-G
• rs4880179
• NM_000954.6:c.18A>G
• PTGDS p.Thr6Thr

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-4 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -4 classification points (ACGS-UK Somatic Oncogenicity v2025). B1_Strong

The ENST00000471521.5(ENSG00000284341):n.18A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Note: ENST00000471521.5 is not a MANE Select or MANE Plus Clinical transcript for ENSG00000284341; the reported annotation may differ from that of the MANE-designated reference transcript for this gene. The variant allele was found at a cumulative frequency of 0.963 (AC=1,542,992) in the gnomAD database across 1,601,766 control chromosomes, including 743,442 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.992. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. The variant has been observed in cBioPortal in 1 sample across 1 study and 1 cancer type; somatic enrichment level: NONE (Observed in at most one deduplicated cBioPortal case.).

• Frequency:
  • Genomes: 𝑓 0.95 (68606 hom., cov: 35)
  • Exomes 𝑓: 0.96 (674836 hom.)
• Consequence: ENSG00000284341 ENST00000471521.5 non_coding_transcript_exon
• 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:):

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -4 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	B1High frequency in general population		GnomAD effective popmax AF >1% — B1 stand-alone benign; GnomAD effective popmax AF = 0.992 — exceeds 1% threshold (B1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: ENST00000471521.5. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	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	Prot: NP_000945.3

PTGDS NM_000954.6

MANE Select

HGVSc / HGVSpc.18A>Gp.Thr6Thr

Exon rankExon 1 of 7

synonymous

Prot: NP_000945.3

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	PTGDS ENST00000371625.8	TSL:1MANE Select	c.18A>G p.Thr6Thr	synonymous	Exon 1 of 7	Prot: ENSP00000360687.3 UniProt:
	ENSG00000284341 ENST00000471521.5	TSL:5	n.18A>G	non_coding_transcript_exon	Exon 1 of 10	Prot: ENSP00000435033.1 UniProt:
	PTGDS ENST00000851752.1		c.18A>G p.Thr6Thr	synonymous	Exon 3 of 9	Prot: ENSP00000521811.1 UniProt:

PTGDS ENST00000371625.8

TSL:1MANE Select

HGVSc / HGVSpc.18A>Gp.Thr6Thr

Exon rankExon 1 of 7

synonymous

Prot: ENSP00000360687.3UniProt: P41222

ENSG00000284341 ENST00000471521.5

TSL:5

HGVSc / HGVSpn.18A>G

Exon rankExon 1 of 10

non_coding_transcript_exon

Prot: ENSP00000435033.1UniProt: P41222

PTGDS ENST00000851752.1

HGVSc / HGVSpc.18A>Gp.Thr6Thr

Exon rankExon 3 of 9

synonymous

Prot: ENSP00000521811.1UniProt: A0ACI8P6N6

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 6 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.949	AC:144402	Hom:68560	AN:152226	Cov:35
GnomAD2 exomes	AF: 0.968	AC:228790	Hom:	AN:236238	Cov:
GnomAD4 exome	AF: 0.965	AC:1398485	Hom:674836	AN:1449422	Cov:43
GnomAD4 genome	AF: 0.949	AC:144507	Hom:68606	AN:152344	Cov:35
TOPMed (Bravo)	AF: 0.947	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.955	AC:156828	Hom:74961	AN:164148	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.956	AC:2239	Hom:1072	AN:2342	Cov:
ChinaMAP Phase 1	AF: 1.00	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.970	AC:291	Hom:	AN:300	Cov:
ESP6500 (Exome Variant Server)	AF: 0.941	AC:12212	Hom:	AN:12982	Cov:
GenomeAsia100K	AF: 0.989	AC:3437	Hom:	AN:3478	Cov:
Qatari Genome	AF: 0.971	AC:1906	Hom:	AN:1964	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 1.00	AC:122642	Hom:61319	AN:122646	Cov:
Turkish Variome	AF: 0.973	AC:6403	Hom:3115	AN:6584	Cov:
UK10K	AF: 0.965	AC:7298	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 1.00	AC:8957	Hom:4477	AN:8960	Cov:

Showing 16 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
ASC(Autism)	0.961 *	1390	1446	0.971 *	6918	7126
BipEx(Bipolar disorder (including schizoaffective))	0.968	27471	28386	0.968	27900	28826
Epi25(Epilepsy)	0.960	40298	41956	0.960	64059	66704
SCHEMA(Schizophrenia)	0.801	61534	76824	0.805	110670	137518

Showing 4 cohortsAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	0.18
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.79
DANN	Benign	0.59
GPN-Star LLR	N/A	4.8
GPN-Star score	N/A	0.64
Mutation Taster	N/A	100/0	polymorphism (auto)
PhyloP100	Benign	-2.7
PromoterAI	N/A	0.022	Neutral

Showing 9 of 9 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.040
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs4880179;

hg19: chr9-139872048;

COSMIC: COSV56400996;

COSMIC: COSV56400996;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar