NM_001098540.3:c.920A>C

Variant names:

• chr4-83309466-T-G
• rs11099592
• NM_001098540.3:c.920A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001098540.3(HPSE):​c.920A>C​(p.Lys307Thr) variant causes a missense change. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K307R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HPSE NM_001098540.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.00
• Publications: 58 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19188878).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPSE	NM_001098540.3	MANE Select	c.920A>C	p.Lys307Thr	missense	Exon 7 of 12	NP_001092010.1
	HPSE	NM_006665.6		c.920A>C	p.Lys307Thr	missense	Exon 8 of 13	NP_006656.2
	HPSE	NM_001199830.1		c.746A>C	p.Lys249Thr	missense	Exon 6 of 11	NP_001186759.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPSE	ENST00000311412.10	TSL:1 MANE Select	c.920A>C	p.Lys307Thr	missense	Exon 7 of 12	ENSP00000308107.5
	HPSE	ENST00000405413.6	TSL:1	c.920A>C	p.Lys307Thr	missense	Exon 8 of 13	ENSP00000384262.2
	HPSE	ENST00000513463.1	TSL:1	c.746A>C	p.Lys249Thr	missense	Exon 6 of 11	ENSP00000421365.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		4.0
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.097
Sift	Benign	0.33	T
Sift4G	Benign	0.41	T
Polyphen		0.73	P
Vest4		0.29
MutPred		0.56		Loss of ubiquitination at K307 (P = 0.0063)
MVP		0.25
MPC		0.26
ClinPred		0.82	D
GERP RS		4.8
Varity_R		0.17
gMVP		0.53
Mutation Taster		=59/41	polymorphism

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

Other links and lift over

dbSNP: rs11099592; hg19: chr4-84230619;