9-136981689-A-C

Position:

• chr9-136981689-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000954.6(PTGDS):​c.*111A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 152,222 control chromosomes in the GnomAD database, including 39,366 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 0.72 (39300 hom., cov: 32)
  • Exomes 𝑓: 0.74 (66 hom.)
• Consequence: PTGDS NM_000954.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.235

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGDS	NM_000954.6	c.*111A>C		3_prime_UTR_variant	7/7	ENST00000371625.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGDS	ENST00000371625.8	c.*111A>C		3_prime_UTR_variant	7/7	1	NM_000954.6	P1
PTGDS	ENST00000444903.2	c.*130A>C		3_prime_UTR_variant	3/3	3
PTGDS	ENST00000446677.2	c.*130A>C		3_prime_UTR_variant	6/6	3
PTGDS	ENST00000492068.2	n.751A>C		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes AF: 0.718 AC: 109105 AN: 151872 Hom.: 39269 Cov.: 32

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.786

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.727

GnomAD4 exome AF: 0.735 AC: 172 AN: 234 Hom.: 66 Cov.: 0 AF XY: 0.753 AC XY: 125 AN XY: 166

Gnomad4 AFR exome AF: 0.750

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.732

Gnomad4 OTH exome AF: 0.778

GnomAD4 genome AF: 0.718 AC: 109188 AN: 151988 Hom.: 39300 Cov.: 32 AF XY: 0.716 AC XY: 53206 AN XY: 74260

Gnomad4 AFR AF: 0.758

Gnomad4 AMR AF: 0.644

Gnomad4 ASJ AF: 0.719

Gnomad4 EAS AF: 0.829

Gnomad4 SAS AF: 0.785

Gnomad4 FIN AF: 0.658

Gnomad4 NFE AF: 0.707

Gnomad4 OTH AF: 0.731

Alfa AF: 0.716 Hom.: 26043

Bravo AF: 0.719

Asia WGS AF: 0.782 AC: 2718 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.8
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs6926; hg19: chr9-139876141;