Variant 4-94302242-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_014485.3(HPGDS):c.339G>C(p.Glu113Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,450,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

HPGDS
NM_014485.3 missense, splice_region

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.40

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05217862).

BP6

Variant 4-94302242-C-G is Benign according to our data. Variant chr4-94302242-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3106798.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPGDS	NM_014485.3 linkuse as main transcript	c.339G>C	p.Glu113Asp	missense_variant, splice_region_variant	5/6	ENST00000295256.10
HPGDS	XM_005262932.4 linkuse as main transcript	c.246G>C	p.Glu82Asp	missense_variant, splice_region_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPGDS	ENST00000295256.10 linkuse as main transcript	c.339G>C	p.Glu113Asp	missense_variant, splice_region_variant	5/6	1	NM_014485.3	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

247146

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133694

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000268

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1450172

Hom.:

Cov.:

AF XY:

0.00000831

AC XY:

AN XY:

721772

show subpopulations

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:

0.0000118

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 27, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.0050

DANN

Benign

0.74

DEOGEN2

Benign

0.042

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.55

M_CAP

Benign

0.0043

MetaRNN

Benign

0.052

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.43

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.4

REVEL

Benign

0.024

Sift

Benign

0.36

Sift4G

Benign

0.34

Polyphen

0.0

Vest4

0.11

MutPred

0.38

Loss of methylation at K108 (P = 0.1164);

MVP

0.088

MPC

0.0088

ClinPred

0.30

GERP RS

-11

Varity_R

0.38

gMVP

0.39

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