dbSNP rs532481270: HPSE:p.Pro482Ser (chr4-83300988-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001098540.3(HPSE):c.1444C>T(p.Pro482Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000187 in 1,606,676 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

HPSE
NM_001098540.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.24

Variant links:

Genes affected

HPSE (HGNC:5164): (heparanase) Heparan sulfate proteoglycans are major components of the basement membrane and extracellular matrix. The protein encoded by this gene is an enzyme that cleaves heparan sulfate proteoglycans to permit cell movement through remodeling of the extracellular matrix. In addition, this cleavage can release bioactive molecules from the extracellular matrix. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

HPSE links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
HPSE	NM_001098540.3 link	c.1444C>T	p.Pro482Ser	missense_variant	Exon 11 of 12	ENST00000311412.10	NP_001092010.1	Q9Y251-1
HPSE	NM_006665.6 link	c.1444C>T	p.Pro482Ser	missense_variant	Exon 12 of 13		NP_006656.2	Q9Y251-1
HPSE	NM_001199830.1 link	c.1270C>T	p.Pro424Ser	missense_variant	Exon 10 of 11		NP_001186759.1	Q9Y251-2
HPSE	NM_001166498.3 link	c.1222C>T	p.Pro408Ser	missense_variant	Exon 10 of 11		NP_001159970.1	Q9Y251-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPSE	ENST00000311412.10 link	c.1444C>T	p.Pro482Ser	missense_variant	Exon 11 of 12	1	NM_001098540.3	ENSP00000308107.5		Q9Y251-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1454456

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723812

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000228

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.00

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

Alfa

AF:

0.0000370

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.030

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.81

D;D;.;.

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.83

.;T;D;T

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.66

D;D;D;D

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.3

M;M;.;.

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-4.5

D;D;D;D

REVEL

Benign

0.21

Sift

Benign

0.078

T;T;T;T

Sift4G

Benign

0.18

T;T;T;T

Polyphen

0.82

P;P;.;.

Vest4

0.67

MVP

0.42

MPC

0.30

ClinPred

0.99

GERP RS

4.6

Varity_R

0.49

gMVP

0.74

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over