9-136979972-G-C

Variant names:

• chr9-136979972-G-C
• NM_000954.6:c.358G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000954.6(PTGDS):​c.358G>C​(p.Val120Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PTGDS NM_000954.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.03

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGDS	NM_000954.6	c.358G>C	p.Val120Leu	missense_variant	Exon 4 of 7	ENST00000371625.8	NP_000945.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGDS	ENST00000371625.8	c.358G>C	p.Val120Leu	missense_variant	Exon 4 of 7	1	NM_000954.6	ENSP00000360687.3
ENSG00000284341	ENST00000471521.5	n.358G>C		non_coding_transcript_exon_variant	Exon 4 of 10	5		ENSP00000435033.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.358G>C (p.V120L) alteration is located in exon 4 (coding exon 4) of the PTGDS gene. This alteration results from a G to C substitution at nucleotide position 358, causing the valine (V) at amino acid position 120 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	.;T;.
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.78	T;.;T
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.70	D;D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Pathogenic	3.4	.;M;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.8	D;D;.
REVEL	Benign	0.26
Sift	Uncertain	0.0060	D;D;.
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	.;D;.
Vest4		0.77
MutPred		0.74		.;Gain of sheet (P = 0.0827);.;
MVP		0.55
MPC		0.97
ClinPred		0.96	D
GERP RS		4.8
Varity_R		0.70
gMVP		0.70

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: chr9-139874424;