Variant 4-94302198-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014485.3(HPGDS):c.383T>C(p.Met128Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0035 in 1,612,780 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0065 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 36 hom. )

Consequence

HPGDS
NM_014485.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.75

Variant links:

Genes affected

HPGDS (HGNC:17890): (hematopoietic prostaglandin D synthase) Prostaglandin-D synthase is a sigma class glutathione-S-transferase family member. The enzyme catalyzes the conversion of PGH2 to PGD2 and plays a role in the production of prostanoids in the immune system and mast cells. The presence of this enzyme can be used to identify the differentiation stage of human megakaryocytes. [provided by RefSeq, Jul 2008]

HPGDS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0071651638).

BP6

Variant 4-94302198-A-G is Benign according to our data. Variant chr4-94302198-A-G is described in ClinVar as [Benign]. Clinvar id is 790395.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00319 (4653/1460522) while in subpopulation MID AF= 0.0432 (249/5764). AF 95% confidence interval is 0.0388. There are 36 homozygotes in gnomad4_exome. There are 2366 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPGDS	NM_014485.3 linkuse as main transcript	c.383T>C	p.Met128Thr	missense_variant	5/6	ENST00000295256.10
HPGDS	XM_005262932.4 linkuse as main transcript	c.290T>C	p.Met97Thr	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPGDS	ENST00000295256.10 linkuse as main transcript	c.383T>C	p.Met128Thr	missense_variant	5/6	1	NM_014485.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00651

AC:

990

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00872

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00558

Gnomad FIN

AF:

0.00169

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.00318

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.00439

AC:

1103

AN:

250982

Hom.:

AF XY:

0.00430

AC XY:

583

AN XY:

135634

show subpopulations

Gnomad AFR exome

AF:

0.0134

Gnomad AMR exome

AF:

0.00495

Gnomad ASJ exome

AF:

0.00655

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00448

Gnomad FIN exome

AF:

0.00254

Gnomad NFE exome

AF:

0.00353

Gnomad OTH exome

AF:

0.00915

GnomAD4 exome

AF:

0.00319

AC:

4653

AN:

1460522

Hom.:

Cov.:

AF XY:

0.00326

AC XY:

2366

AN XY:

726588

show subpopulations

Gnomad4 AFR exome

AF:

0.0143

Gnomad4 AMR exome

AF:

0.00557

Gnomad4 ASJ exome

AF:

0.00675

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00472

Gnomad4 FIN exome

AF:

0.00215

Gnomad4 NFE exome

AF:

0.00237

Gnomad4 OTH exome

AF:

0.00564

GnomAD4 genome

AF:

0.00653

AC:

995

AN:

152258

Hom.:

Cov.:

AF XY:

0.00685

AC XY:

510

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0127

Gnomad4 AMR

AF:

0.00871

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00559

Gnomad4 FIN

AF:

0.00169

Gnomad4 NFE

AF:

0.00318

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.00467

Hom.:

Bravo

AF:

0.00740

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.0125

AC:

ESP6500EA

AF:

0.00477

AC:

ExAC

AF:

0.00471

AC:

572

Asia WGS

AF:

0.00405

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 08, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.60

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.073

Eigen

Benign

-0.15

Eigen_PC

Benign

0.061

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.70

MetaRNN

Benign

0.0072

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.14

MutationTaster

Benign

0.77

PrimateAI

Benign

0.42

PROVEAN

Benign

-2.2

REVEL

Benign

0.14

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.030

Polyphen

0.013

Vest4

0.51

MVP

0.20

MPC

0.014

ClinPred

0.079

GERP RS

5.5

Varity_R

0.71

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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