Variant 9-136978985-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000954.6(PTGDS):c.115-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00543 in 1,604,724 control chromosomes in the GnomAD database, including 422 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 225 hom., cov: 33)

Exomes 𝑓: 0.0030 ( 197 hom. )

Consequence

PTGDS
NM_000954.6 splice_region, intron

Scores

Splicing: ADA: 0.00001359

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.899

Variant links:

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]

PTGDS links:

ENSG00000284341 (HGNC:):

ENSG00000284341 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 9-136978985-C-T is Benign according to our data. Variant chr9-136978985-C-T is described in ClinVar as [Benign]. Clinvar id is 768341.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGDS	NM_000954.6 linkuse as main transcript	c.115-8C>T		splice_region_variant, intron_variant		ENST00000371625.8	NP_000945.3	P41222A0A024R8G3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGDS	ENST00000371625.8 linkuse as main transcript	c.115-8C>T		splice_region_variant, intron_variant		1	NM_000954.6	ENSP00000360687.3		P41222
ENSG00000284341	ENST00000471521.5 linkuse as main transcript	n.115-8C>T		splice_region_variant, intron_variant		5		ENSP00000435033.1

Frequencies

GnomAD3 genomes

AF:

0.0288

AC:

4369

AN:

151514

Hom.:

225

Cov.:

show subpopulations

Gnomad AFR

AF:

0.100

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000417

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00968

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.0206

GnomAD3 exomes

AF:

0.00741

AC:

1733

AN:

233732

Hom.:

AF XY:

0.00544

AC XY:

697

AN XY:

128204

show subpopulations

Gnomad AFR exome

AF:

0.101

Gnomad AMR exome

AF:

0.00447

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000132

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000222

Gnomad OTH exome

AF:

0.00397

GnomAD4 exome

AF:

0.00298

AC:

4337

AN:

1453088

Hom.:

197

Cov.:

AF XY:

0.00252

AC XY:

1821

AN XY:

722878

show subpopulations

Gnomad4 AFR exome

AF:

0.106

Gnomad4 AMR exome

AF:

0.00554

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000100

Gnomad4 OTH exome

AF:

0.00657

GnomAD4 genome

AF:

0.0289

AC:

4376

AN:

151636

Hom.:

225

Cov.:

AF XY:

0.0284

AC XY:

2102

AN XY:

74064

show subpopulations

Gnomad4 AFR

AF:

0.100

Gnomad4 AMR

AF:

0.0111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000418

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.0204

Alfa

AF:

0.00521

Hom.:

Bravo

AF:

0.0328

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.7

DANN

Benign

0.96

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000014

dbscSNV1_RF

Benign

0.026

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over