3-50299991-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 24 publications found

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]

HYAL1 Gene-Disease associations (from GenCC):

• mucopolysaccharidosis type 9

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, G2P

ENSG00000295204 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033159.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYAL1	NM_033159.4	MANE Select	c.*492C>T		3_prime_UTR	Exon 4 of 4	NP_149349.2
	HYAL1	NM_153281.2		c.*492C>T		3_prime_UTR	Exon 6 of 6	NP_695013.1	Q12794-1
	HYAL1	NM_153282.3		c.*492C>T		3_prime_UTR	Exon 3 of 3	NP_695014.1	Q12794-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYAL1	ENST00000395144.7	TSL:1 MANE Select	c.*492C>T		3_prime_UTR	Exon 4 of 4	ENSP00000378576.2	Q12794-1
	HYAL1	ENST00000266031.8	TSL:1	c.*492C>T		3_prime_UTR	Exon 3 of 3	ENSP00000266031.4	Q12794-1
	HYAL1	ENST00000320295.12	TSL:2	c.*492C>T		3_prime_UTR	Exon 6 of 6	ENSP00000346068.5	Q12794-1

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

African (AFR) AF: 0.0122 AC: 35 AN: 2874

American (AMR) AF: 0.0601 AC: 258 AN: 4294

Ashkenazi Jewish (ASJ) AF: 0.0728 AC: 124 AN: 1704

East Asian (EAS) AF: 0.00 AC: 0 AN: 4352

South Asian (SAS) AF: 0.0239 AC: 308 AN: 12876

European-Finnish (FIN) AF: 0.0604 AC: 109 AN: 1804

Middle Eastern (MID) AF: 0.126 AC: 33 AN: 262

European-Non Finnish (NFE) AF: 0.0949 AC: 4226 AN: 44526

Other (OTH) AF: 0.0778 AC: 292 AN: 3752

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

African (AFR) AF: 0.0182 AC: 758 AN: 41580

American (AMR) AF: 0.0775 AC: 1185 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0786 AC: 273 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5188

South Asian (SAS) AF: 0.0193 AC: 93 AN: 4826

European-Finnish (FIN) AF: 0.0439 AC: 466 AN: 10610

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7083 AN: 68016

Other (OTH) AF: 0.0810 AC: 171 AN: 2112

Alfa AF: 0.0932 Hom.: 1366

Bravo AF: 0.0673

Asia WGS AF: 0.00982 AC: 34 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Deficiency of hyaluronoglucosaminidase (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.5
DANN	Benign	0.73
PhyloP100		-0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1283; hg19: chr3-50337422;