3-50295071-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_003549.4(HYAL3):c.532C>T(p.Arg178Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000471 in 1,613,140 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R178H) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000050 ( 0 hom. )
Consequence
HYAL3
NM_003549.4 missense
NM_003549.4 missense
Scores
6
6
5
Clinical Significance
Conservation
PhyloP100: 4.75
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 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HYAL3 | NM_003549.4 | c.532C>T | p.Arg178Cys | missense_variant | 2/4 | ENST00000336307.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HYAL3 | ENST00000336307.6 | c.532C>T | p.Arg178Cys | missense_variant | 2/4 | 1 | NM_003549.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152222Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000798 AC: 2AN: 250618Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135558
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GnomAD4 exome AF: 0.0000500 AC: 73AN: 1460918Hom.: 0 Cov.: 30 AF XY: 0.0000537 AC XY: 39AN XY: 726690
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152222Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74366
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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 | Feb 24, 2023 | The c.532C>T (p.R178C) alteration is located in exon 2 (coding exon 1) of the HYAL3 gene. This alteration results from a C to T substitution at nucleotide position 532, causing the arginine (R) at amino acid position 178 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
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Pathogenic
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;M;M;M
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D;.;D
REVEL
Uncertain
Sift
Pathogenic
D;T;.;D
Sift4G
Uncertain
D;D;D;D
Polyphen
D;D;D;D
Vest4
MVP
MPC
1.2
ClinPred
D
GERP RS
Varity_R
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