Variant 14-52268398-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000953.3(PTGDR):c.584C>T(p.Ser195Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000236 in 1,611,572 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

PTGDR
NM_000953.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.454

Variant links:

Genes affected

PTGDR (HGNC:9591): (prostaglandin D2 receptor) This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor (GPCR) superfamily. The receptors are seven-pass transmembrane proteins that respond to extracellular cues and activate intracellular signal transduction pathways. This protein is reported to be a receptor for prostaglandin D2, which is a mediator of allergic inflammation and allergic airway inflammation in asthma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

PTGDR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.081184685).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGDR	NM_000953.3 linkuse as main transcript	c.584C>T	p.Ser195Leu	missense_variant	1/2	ENST00000306051.3	NP_000944.1	Q13258-1
PTGDR	NM_001281469.2 linkuse as main transcript	c.584C>T	p.Ser195Leu	missense_variant	1/3		NP_001268398.1	Q13258-2
PTGDR	XM_005267891.5 linkuse as main transcript	c.584C>T	p.Ser195Leu	missense_variant	1/3		XP_005267948.1	Q13258-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGDR	ENST00000306051.3 linkuse as main transcript	c.584C>T	p.Ser195Leu	missense_variant	1/2	1	NM_000953.3	ENSP00000303424.2		Q13258-1
PTGDR	ENST00000553372.1 linkuse as main transcript	c.584C>T	p.Ser195Leu	missense_variant	1/3	3		ENSP00000452408.1		Q13258-2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000961

AC:

AN:

249650

Hom.:

AF XY:

0.0000962

AC XY:

AN XY:

135146

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000636

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000240

AC:

AN:

1459328

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

726114

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000648

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000642

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2024

The c.584C>T (p.S195L) alteration is located in exon 1 (coding exon 1) of the PTGDR gene. This alteration results from a C to T substitution at nucleotide position 584, causing the serine (S) at amino acid position 195 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

Benign

0.097

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

T;.

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.0088

MetaRNN

Benign

0.081

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;L

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.064

Sift

Benign

0.19

T;T

Sift4G

Benign

0.33

T;T

Polyphen

0.10

B;.

Vest4

0.25

MutPred

0.54

Loss of disorder (P = 0.0146);Loss of disorder (P = 0.0146);

MVP

0.46

MPC

0.62

ClinPred

0.079

GERP RS

3.6

Varity_R

0.30

gMVP

0.52

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

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