rs3774753

Positions:

• chr3-50296196-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.-17-577A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,076 control chromosomes in the GnomAD database, including 6,849 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 0.21 (6849 hom., cov: 32)
• Consequence: HYAL3 NM_003549.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.953

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=-0.87).
• 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	Protein	UniProt
HYAL3	NM_003549.4	c.-17-577A>G		intron_variant		ENST00000336307.6	NP_003540.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HYAL3	ENST00000336307.6	c.-17-577A>G		intron_variant		1	NM_003549.4	ENSP00000337425.1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31853 AN: 151958 Hom.: 6839 Cov.: 32

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.0675

Gnomad FIN AF: 0.0507

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0301

Gnomad OTH AF: 0.185

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.210 AC: 31904 AN: 152076 Hom.: 6849 Cov.: 32 AF XY: 0.214 AC XY: 15874 AN XY: 74340

Gnomad4 AFR AF: 0.482

Gnomad4 AMR AF: 0.330

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.599

Gnomad4 SAS AF: 0.0673

Gnomad4 FIN AF: 0.0507

Gnomad4 NFE AF: 0.0301

Gnomad4 OTH AF: 0.185

Alfa AF: 0.134 Hom.: 609

Bravo AF: 0.250

Asia WGS AF: 0.238 AC: 827 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.57
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs3774753; hg19: chr3-50333627;