chr3-50295202-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_003549.4(HYAL3):āc.401T>Cā(p.Leu134Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 33)
Consequence
HYAL3
NM_003549.4 missense
NM_003549.4 missense
Scores
5
8
4
Clinical Significance
Conservation
PhyloP100: 5.03
Genes affected
HYAL3 (HGNC:5322): (hyaluronidase 3) This gene encodes a member of the hyaluronidase family. Hyaluronidases are endoglycosidase enzymes that degrade hyaluronan, one of the major glycosaminoglycans of the extracellular matrix. The regulated turnover of hyaluronan plays a critical role in many biological processes including cell proliferation, migration and differentiation. The encoded protein may also play an important role in sperm function. This gene is one of several related genes in a region of chromosome 3p21.3 associated with tumor suppression, and the expression of specific transcript variants may be indicative of tumor status. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and some isoforms may lack hyaluronidase activity. This gene overlaps and is on the same strand as N-acetyltransferase 6 (GCN5-related), and some transcripts of each gene share a portion of the first exon. [provided by RefSeq, Jan 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.814
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HYAL3 | NM_003549.4 | c.401T>C | p.Leu134Pro | missense_variant | 2/4 | ENST00000336307.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HYAL3 | ENST00000336307.6 | c.401T>C | p.Leu134Pro | missense_variant | 2/4 | 1 | NM_003549.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152180Hom.: 0 Cov.: 33
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GnomAD4 exome Cov.: 31
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152180Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74356
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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 | Jan 24, 2024 | The c.401T>C (p.L134P) alteration is located in exon 2 (coding exon 1) of the HYAL3 gene. This alteration results from a T to C substitution at nucleotide position 401, causing the leucine (L) at amino acid position 134 to be replaced by a proline (P). 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
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;M;M;M;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;.;D;D
REVEL
Uncertain
Sift
Benign
T;D;.;T;D
Sift4G
Uncertain
D;D;D;D;.
Polyphen
D;D;D;D;.
Vest4
MutPred
Gain of catalytic residue at L134 (P = 0.0293);Gain of catalytic residue at L134 (P = 0.0293);Gain of catalytic residue at L134 (P = 0.0293);Gain of catalytic residue at L134 (P = 0.0293);Gain of catalytic residue at L134 (P = 0.0293);
MVP
MPC
1.4
ClinPred
D
GERP RS
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gMVP
Splicing
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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