rs2071204

chr3-50293556-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003549.4(HYAL3):c.985-41A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0431 in 1,611,666 control chromosomes in the GnomAD database, including 12,981 homozygotes. 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: 𝑓 0.10 (2267 hom., cov: 33)
  • Exomes 𝑓: 0.037 (10714 hom.)
• Consequence: HYAL3 NM_003549.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.260

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HYAL3	NM_003549.4	c.985-41A>G		intron_variant		ENST00000336307.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HYAL3	ENST00000336307.6	c.985-41A>G		intron_variant		1	NM_003549.4	P1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15713 AN: 152142 Hom.: 2265 Cov.: 33

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.0211

Gnomad FIN AF: 0.0468

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00359

Gnomad OTH AF: 0.0865

GnomAD3 exomes AF: 0.122 AC: 30393 AN: 250048 Hom.: 7026 AF XY: 0.0990 AC XY: 13376 AN XY: 135154

Gnomad AFR exome AF: 0.177

Gnomad AMR exome AF: 0.412

Gnomad ASJ exome AF: 0.00332

Gnomad EAS exome AF: 0.614

Gnomad SAS exome AF: 0.00894

Gnomad FIN exome AF: 0.0446

Gnomad NFE exome AF: 0.00352

Gnomad OTH exome AF: 0.0676

GnomAD4 exome AF: 0.0368 AC: 53716 AN: 1459406 Hom.: 10714 Cov.: 32 AF XY: 0.0333 AC XY: 24171 AN XY: 725636

Gnomad4 AFR exome AF: 0.193

Gnomad4 AMR exome AF: 0.389

Gnomad4 ASJ exome AF: 0.00426

Gnomad4 EAS exome AF: 0.535

Gnomad4 SAS exome AF: 0.0102

Gnomad4 FIN exome AF: 0.0440

Gnomad4 NFE exome AF: 0.00173

Gnomad4 OTH exome AF: 0.0565

GnomAD4 genome AF: 0.103 AC: 15743 AN: 152260 Hom.: 2267 Cov.: 33 AF XY: 0.110 AC XY: 8185 AN XY: 74452

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.599

Gnomad4 SAS AF: 0.0209

Gnomad4 FIN AF: 0.0468

Gnomad4 NFE AF: 0.00359

Gnomad4 OTH AF: 0.0870

Alfa AF: 0.0738 Hom.: 354

Bravo AF: 0.129

Asia WGS AF: 0.206 AC: 713 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.63
Dann	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs2071204; hg19: chr3-50330987; COSMIC: COSV104411889; COSMIC: COSV104411889;