3-50299991-G-A

Variant names:

• chr3-50299991-G-A
• rs1283
• NM_033159.4:c.*492C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_033159.4(HYAL1):​c.*492C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0677 in 228,750 control chromosomes in the GnomAD database, including 771 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.066 (494 hom., cov: 33)
  • Exomes 𝑓: 0.070 (277 hom.)
• Consequence: HYAL1 NM_033159.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.611

Genes affected

HYAL1 (HGNC:5320): (hyaluronidase 1) This gene encodes a lysosomal hyaluronidase. Hyaluronidases intracellularly degrade hyaluronan, one of the major glycosaminoglycans of the extracellular matrix. Hyaluronan is thought to be involved in cell proliferation, migration and differentiation. This enzyme is active at an acidic pH and is the major hyaluronidase in plasma. Mutations in this gene are associated with mucopolysaccharidosis type IX, or hyaluronidase deficiency. The gene is one of several related genes in a region of chromosome 3p21.3 associated with tumor suppression. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 3-50299991-G-A is Benign according to our data. Variant chr3-50299991-G-A is described in ClinVar as [Benign]. Clinvar id is 346077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYAL1	NM_033159.4	c.*492C>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000395144.7	NP_149349.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HYAL1	ENST00000395144	c.*492C>T		3_prime_UTR_variant	Exon 4 of 4	1	NM_033159.4	ENSP00000378576.2
HYAL1	ENST00000266031	c.*492C>T		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000266031.4
HYAL1	ENST00000320295	c.*492C>T		3_prime_UTR_variant	Exon 6 of 6	2		ENSP00000346068.5
HYAL1	ENST00000618175	c.*492C>T		3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000477903.1

Frequencies

GnomAD3 genomes AF: 0.0664 AC: 10106 AN: 152188 Hom.: 494 Cov.: 33

Gnomad AFR AF: 0.0183

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0776

Gnomad ASJ AF: 0.0786

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0193

Gnomad FIN AF: 0.0439

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.0823

GnomAD4 exome AF: 0.0704 AC: 5385 AN: 76444 Hom.: 277 Cov.: 0 AF XY: 0.0645 AC XY: 2653 AN XY: 41152

Gnomad4 AFR exome AF: 0.0122

Gnomad4 AMR exome AF: 0.0601

Gnomad4 ASJ exome AF: 0.0728

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0239

Gnomad4 FIN exome AF: 0.0604

Gnomad4 NFE exome AF: 0.0949

Gnomad4 OTH exome AF: 0.0778

GnomAD4 genome AF: 0.0663 AC: 10101 AN: 152306 Hom.: 494 Cov.: 33 AF XY: 0.0617 AC XY: 4594 AN XY: 74480

Gnomad4 AFR AF: 0.0182

Gnomad4 AMR AF: 0.0775

Gnomad4 ASJ AF: 0.0786

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0193

Gnomad4 FIN AF: 0.0439

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.0810

Alfa AF: 0.0974 Hom.: 904

Bravo AF: 0.0673

Asia WGS AF: 0.00982 AC: 34 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Deficiency of hyaluronoglucosaminidase Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.5
DANN	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1283; hg19: chr3-50337422;