4-83295215-C-T

Variant names:

• chr4-83295215-C-T
• rs6856901
• NM_001098540.3:c.*129G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001098540.3(HPSE):​c.*129G>A variant causes a 3 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HPSE NM_001098540.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• Publications: 7 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

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.*129G>A		3_prime_UTR	Exon 12 of 12	NP_001092010.1	Q9Y251-1
	HPSE	NM_006665.6		c.*129G>A		3_prime_UTR	Exon 13 of 13	NP_006656.2	Q9Y251-1
	HPSE	NM_001199830.1		c.*129G>A		3_prime_UTR	Exon 11 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.*129G>A		3_prime_UTR	Exon 12 of 12	ENSP00000308107.5	Q9Y251-1
	HPSE	ENST00000405413.6	TSL:1	c.*129G>A		3_prime_UTR	Exon 13 of 13	ENSP00000384262.2	Q9Y251-1
	HPSE	ENST00000681769.1		c.1473-1620G>A		intron	N/A	ENSP00000506434.1	A0A7P0TBD9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 493454 Hom.: 0 Cov.: 7 AF XY: 0.00 AC XY: 0 AN XY: 259296

African (AFR) AF: 0.00 AC: 0 AN: 13798

American (AMR) AF: 0.00 AC: 0 AN: 21844

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13334

East Asian (EAS) AF: 0.00 AC: 0 AN: 32932

South Asian (SAS) AF: 0.00 AC: 0 AN: 38544

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34830

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1954

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 309352

Other (OTH) AF: 0.00 AC: 0 AN: 26866

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 208

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.5

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

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

Other links and lift over

dbSNP: rs6856901; hg19: chr4-84216368;