rs373648825

Variant names:

• chr4-83295426-C-G
• rs373648825
• NM_001098540.3:c.1550G>C

Your query was ambiguous. Multiple possible variants found:

• chr4-83295426-C-G
• chr4-83295426-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001098540.3(HPSE):​c.1550G>C​(p.Arg517Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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: not found (cov: 32)
• Consequence: HPSE NM_001098540.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054196656).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPSE	NM_001098540.3	c.1550G>C	p.Arg517Pro	missense_variant	Exon 12 of 12	ENST00000311412.10	NP_001092010.1
HPSE	NM_006665.6	c.1550G>C	p.Arg517Pro	missense_variant	Exon 13 of 13		NP_006656.2
HPSE	NM_001199830.1	c.1376G>C	p.Arg459Pro	missense_variant	Exon 11 of 11		NP_001186759.1
HPSE	NM_001166498.3	c.1328G>C	p.Arg443Pro	missense_variant	Exon 11 of 11		NP_001159970.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPSE	ENST00000311412.10	c.1550G>C	p.Arg517Pro	missense_variant	Exon 12 of 12	1	NM_001098540.3	ENSP00000308107.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Benign	0.93
DEOGEN2	Benign	0.29	T;T;.;.
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.65	.;T;T;T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.054	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;L;.;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.2	N;N;N;N
REVEL	Benign	0.018
Sift	Benign	0.42	T;T;T;T
Sift4G	Benign	0.42	T;T;T;T
Polyphen		0.0010	B;B;.;.
Vest4		0.13
MutPred		0.36		Gain of catalytic residue at R517 (P = 0.0102);Gain of catalytic residue at R517 (P = 0.0102);.;.;
MVP		0.11
MPC		0.13
ClinPred		0.17	T
GERP RS		2.7
Varity_R		0.60
gMVP		0.65

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

Other links and lift over

dbSNP: rs373648825; hg19: chr4-84216579;