dbSNP rs34124298: HPGDS:p.Met128Thr (chr4-94302198-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

9 publications found

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

new If you want to explore the variant's impact on the transcript NM_014485.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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. GnomAdExome4 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 GnomAdExome4. There are 2366 alleles in the male GnomAdExome4 subpopulation. Median coverage is 29. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014485.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPGDS	NM_014485.3	MANE Select	c.383T>C	p.Met128Thr	missense	Exon 5 of 6	NP_055300.1	A0A384P5J0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPGDS	ENST00000295256.10	TSL:1 MANE Select	c.383T>C	p.Met128Thr	missense	Exon 5 of 6	ENSP00000295256.5	O60760
	HPGDS	ENST00000944232.1		c.290T>C	p.Met97Thr	missense	Exon 4 of 5	ENSP00000614291.1

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

GnomAD2 exomes

AF:

0.00439

AC:

1103

AN:

250982

AF XY:

0.00430

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 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

African (AFR)

AF:

0.0143

AC:

479

AN:

33420

American (AMR)

AF:

0.00557

AC:

249

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00675

AC:

176

AN:

26092

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39588

South Asian (SAS)

AF:

0.00472

AC:

407

AN:

86164

European-Finnish (FIN)

AF:

0.00215

AC:

115

AN:

53404

Middle Eastern (MID)

AF:

0.0432

AC:

249

AN:

5764

European-Non Finnish (NFE)

AF:

0.00237

AC:

2637

AN:

1111064

Other (OTH)

AF:

0.00564

AC:

340

AN:

60324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

211

422

633

844

1055

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

188

282

376

470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00653

AC:

995

AN:

152258

Hom.:

Cov.:

AF XY:

0.00685

AC XY:

510

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0127

AC:

526

AN:

41544

American (AMR)

AF:

0.00871

AC:

133

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00720

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.00559

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00169

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00318

AC:

216

AN:

68004

Other (OTH)

AF:

0.0156

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

148

197

246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00496

Hom.:

Bravo

AF:

0.00740

Asia WGS

AF:

0.00405

AC:

AN:

3474

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.60

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Uncertain

(source)

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

PhyloP100

5.8

PrimateAI

Benign

0.42

PROVEAN

Benign

-2.2

REVEL

Benign

0.14

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.030

Varity_R

0.71

gMVP

0.68

Mutation Taster

=86/14

polymorphism

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over