rs12512551

Variant names:

• chr4-83310866-G-A
• rs12512551
• NM_001098540.3:c.698C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-83310866-G-A
• chr4-83310866-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001098540.3(HPSE):​c.698C>T​(p.Ala233Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,102 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: HPSE NM_001098540.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.08
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30245468).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPSE	NM_001098540.3	c.698C>T	p.Ala233Val	missense_variant	Exon 5 of 12	ENST00000311412.10	NP_001092010.1
HPSE	NM_006665.6	c.698C>T	p.Ala233Val	missense_variant	Exon 6 of 13		NP_006656.2
HPSE	NM_001199830.1	c.524C>T	p.Ala175Val	missense_variant	Exon 4 of 11		NP_001186759.1
HPSE	NM_001166498.3	c.698C>T	p.Ala233Val	missense_variant	Exon 6 of 11		NP_001159970.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPSE	ENST00000311412.10	c.698C>T	p.Ala233Val	missense_variant	Exon 5 of 12	1	NM_001098540.3	ENSP00000308107.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461102 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726916

African (AFR) AF: 0.00 AC: 0 AN: 33444

American (AMR) AF: 0.00 AC: 0 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111458

Other (OTH) AF: 0.00 AC: 0 AN: 60362

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T;T;.;.
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	.;D;D;D
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.30	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L;L;L;.
PhyloP100		7.1
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.8	N;N;N;N
REVEL	Benign	0.18
Sift	Benign	0.69	T;T;T;T
Sift4G	Benign	0.51	T;T;T;T
Polyphen		1.0	D;D;.;.
Vest4		0.28
MutPred		0.52		Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);.;
MVP		0.60
MPC		0.14
ClinPred		0.93	D
GERP RS		5.2
Varity_R		0.35
gMVP		0.65
Mutation Taster		=64/36	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs12512551; hg19: chr4-84232019;