chr4-83310773-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001098540.3(HPSE):c.791A>G(p.Tyr264Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000315 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.000031 ( 0 hom. )
Consequence
HPSE
NM_001098540.3 missense
NM_001098540.3 missense
Scores
1
11
6
Clinical Significance
Conservation
PhyloP100: 1.42
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HPSE | NM_001098540.3 | c.791A>G | p.Tyr264Cys | missense_variant | 5/12 | ENST00000311412.10 | |
HPSE | NM_006665.6 | c.791A>G | p.Tyr264Cys | missense_variant | 6/13 | ||
HPSE | NM_001199830.1 | c.617A>G | p.Tyr206Cys | missense_variant | 4/11 | ||
HPSE | NM_001166498.3 | c.791A>G | p.Tyr264Cys | missense_variant | 6/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HPSE | ENST00000311412.10 | c.791A>G | p.Tyr264Cys | missense_variant | 5/12 | 1 | NM_001098540.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251462Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135898
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GnomAD4 exome AF: 0.0000315 AC: 46AN: 1461874Hom.: 0 Cov.: 31 AF XY: 0.0000371 AC XY: 27AN XY: 727236
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GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
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31
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TwinsUK
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1
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 06, 2022 | The c.791A>G (p.Y264C) alteration is located in exon 6 (coding exon 5) of the HPSE gene. This alteration results from a A to G substitution at nucleotide position 791, causing the tyrosine (Y) at amino acid position 264 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
D;D;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
D;D;.;.
Vest4
MutPred
Gain of methylation at K262 (P = 0.0811);Gain of methylation at K262 (P = 0.0811);Gain of methylation at K262 (P = 0.0811);.;
MVP
MPC
0.22
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at