9-136977596-A-T

Variant names:

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

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-3 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -3 classification points (ACMG Germline Pathogenicity v2019). PM2BP4_StrongBP7

The NM_000954.6(PTGDS):c.18A>T (p.Thr6Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. 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.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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:):

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -3 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Absent from gnomAD (AR/unknown gene) — PM2; Absent from gnomAD at well-covered site (MOI: unknown) (threshold 0.001) — PM2 moderate.
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).
	BP7Synonymous variant, no splicing impact		Synonymous variant at non-conserved position with no predicted splicing impact (BP7); Synonymous at non-conserved position, no splicing concern — benign (BP7).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_000954.6. 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>T p.Thr6Thr	synonymous	Exon 1 of 7	Prot: NP_000945.3

PTGDS NM_000954.6

MANE Select

HGVSc / HGVSpc.18A>Tp.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>T p.Thr6Thr	synonymous	Exon 1 of 7	Prot: ENSP00000360687.3 UniProt:
	ENSG00000284341 ENST00000471521.5	TSL:5	n.18A>T	non_coding_transcript_exon	Exon 1 of 10	Prot: ENSP00000435033.1 UniProt:
	PTGDS ENST00000851752.1		c.18A>T p.Thr6Thr	synonymous	Exon 3 of 9	Prot: ENSP00000521811.1 UniProt:

PTGDS ENST00000371625.8

TSL:1MANE Select

HGVSc / HGVSpc.18A>Tp.Thr6Thr

Exon rankExon 1 of 7

synonymous

Prot: ENSP00000360687.3UniProt: P41222

ENSG00000284341 ENST00000471521.5

TSL:5

HGVSc / HGVSpn.18A>T

Exon rankExon 1 of 10

non_coding_transcript_exon

Prot: ENSP00000435033.1UniProt: P41222

PTGDS ENST00000851752.1

HGVSc / HGVSpc.18A>Tp.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 3 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:35
GnomAD4 exome Warning	AF: 0.00	AC:0	Hom:0	AN:1449638	Cov:43
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:35

Showing 3 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	0.13
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.65
DANN	Benign	0.72
GPN-Star LLR	N/A	1.3
GPN-Star score	N/A	-1.3
PhyloP100	Benign	-2.7
PromoterAI	N/A	-0.029	Neutral

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
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;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar