chr4-83308879-G-G

Variant names:

• chr4-83308879-G-G
• NM_001098540.3:c.

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001098540.3(HPSE):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.31
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098540.3. 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
	HPSE	NM_001098540.3	MANE Select	c.		exon_region	Exon 8 of 12	NP_001092010.1	Q9Y251-1
	HPSE	NM_006665.6		c.		exon_region	Exon 9 of 13	NP_006656.2	Q9Y251-1
	HPSE	NM_001199830.1		c.		exon_region	Exon 7 of 11	NP_001186759.1	Q9Y251-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPSE	ENST00000311412.10	TSL:1 MANE Select	c.		exon_region	Exon 8 of 12	ENSP00000308107.5	Q9Y251-1
	HPSE	ENST00000405413.6	TSL:1	c.		exon_region	Exon 9 of 13	ENSP00000384262.2	Q9Y251-1
	HPSE	ENST00000513463.1	TSL:1	c.		exon_region	Exon 7 of 11	ENSP00000421365.1	Q9Y251-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-4.3

Splicing

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.

Other links and lift over

hg19: chr4-84230032;