NM_000954.6:c.166C>G

Variant names:

• chr9-136979044-C-G
• NM_000954.6:c.166C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000954.6(PTGDS):​c.166C>G​(p.Arg56Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,456,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R56Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PTGDS NM_000954.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29240617).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGDS	NM_000954.6	c.166C>G	p.Arg56Gly	missense_variant	Exon 2 of 7	ENST00000371625.8	NP_000945.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGDS	ENST00000371625.8	c.166C>G	p.Arg56Gly	missense_variant	Exon 2 of 7	1	NM_000954.6	ENSP00000360687.3
ENSG00000284341	ENST00000471521.5	n.166C>G		non_coding_transcript_exon_variant	Exon 2 of 10	5		ENSP00000435033.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1456388 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 724080

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Uncertain	0.97
DEOGEN2	Benign	0.21	.;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.73	T;.
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.7	.;L
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.7	D;D
REVEL	Benign	0.082
Sift	Uncertain	0.015	D;D
Sift4G	Uncertain	0.054	T;T
Polyphen		0.29	.;B
Vest4		0.12
MutPred		0.54		Loss of MoRF binding (P = 0.0075);Loss of MoRF binding (P = 0.0075);
MVP		0.31
MPC		0.99
ClinPred		0.97	D
GERP RS		3.4
Varity_R		0.55
gMVP		0.60

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-139873496;