chr9-136980066-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000954.6(PTGDS):​c.448+4C>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000553 in 1,610,182 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 3 hom., cov: 33)
Exomes 𝑓: 0.00028 ( 2 hom. )

Consequence

PTGDS
NM_000954.6 splice_donor_region, intron

Scores

2
Splicing: ADA: 0.0004218
2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.958
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 9-136980066-C-T is Benign according to our data. Variant chr9-136980066-C-T is described in ClinVar as [Benign]. Clinvar id is 785302.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PTGDSNM_000954.6 linkuse as main transcriptc.448+4C>T splice_donor_region_variant, intron_variant ENST00000371625.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PTGDSENST00000371625.8 linkuse as main transcriptc.448+4C>T splice_donor_region_variant, intron_variant 1 NM_000954.6 P1

Frequencies

GnomAD3 genomes
AF:
0.00316
AC:
480
AN:
152114
Hom.:
3
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0112
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000523
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.000784
AC:
194
AN:
247460
Hom.:
2
AF XY:
0.000568
AC XY:
76
AN XY:
133868
show subpopulations
Gnomad AFR exome
AF:
0.0107
Gnomad AMR exome
AF:
0.000379
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000627
Gnomad OTH exome
AF:
0.000331
GnomAD4 exome
AF:
0.000281
AC:
409
AN:
1457950
Hom.:
2
Cov.:
31
AF XY:
0.000226
AC XY:
164
AN XY:
725258
show subpopulations
Gnomad4 AFR exome
AF:
0.0101
Gnomad4 AMR exome
AF:
0.000516
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000385
Gnomad4 NFE exome
AF:
0.0000108
Gnomad4 OTH exome
AF:
0.000547
GnomAD4 genome
AF:
0.00316
AC:
481
AN:
152232
Hom.:
3
Cov.:
33
AF XY:
0.00305
AC XY:
227
AN XY:
74432
show subpopulations
Gnomad4 AFR
AF:
0.0112
Gnomad4 AMR
AF:
0.000523
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.000580
Hom.:
0
Bravo
AF:
0.00324
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpApr 03, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
1.1
DANN
Benign
0.91

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00042
dbscSNV1_RF
Benign
0.056
SpliceAI score (max)
0.060
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.

Other links and lift over

dbSNP: rs147964178; hg19: chr9-139874518; API