rs12488302

Variant names:

• chr3-50303895-C-T
• rs12488302
• NM_153281.2:c.-132G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-50303895-C-T
• chr3-50303895-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_153281.2(HYAL1):​c.-132G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.054 in 152,224 control chromosomes in the GnomAD database, including 1,552 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.054 (1552 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HYAL1 NM_153281.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.895
• Publications: 4 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: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Genomics England PanelApp, Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 3-50303895-C-T is Benign according to our data. Variant chr3-50303895-C-T is described in ClinVar as Benign. ClinVar VariationId is 346093.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153281.2. 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_153281.2		c.-132G>A		5_prime_UTR_premature_start_codon_gain	Exon 3 of 6	NP_695013.1	Q12794-1
	HYAL1	NM_153281.2		c.-132G>A		5_prime_UTR	Exon 3 of 6	NP_695013.1	Q12794-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYAL1	ENST00000320295.12	TSL:2	c.-132G>A		5_prime_UTR_premature_start_codon_gain	Exon 3 of 6	ENSP00000346068.5	Q12794-1
	HYAL1	ENST00000618175.4	TSL:5	c.-132G>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	ENSP00000477903.1	Q12794-1
	HYAL1	ENST00000907773.1		c.-230G>A		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	ENSP00000577832.1

Frequencies

GnomAD3 genomes AF: 0.0540 AC: 8211 AN: 152106 Hom.: 1551 Cov.: 32

Gnomad AFR AF: 0.00804

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.0190

Gnomad FIN AF: 0.0511

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00349

Gnomad OTH AF: 0.0564

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 18 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 16

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 10

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.0540 AC: 8218 AN: 152224 Hom.: 1552 Cov.: 32 AF XY: 0.0623 AC XY: 4635 AN XY: 74420

African (AFR) AF: 0.00801 AC: 333 AN: 41548

American (AMR) AF: 0.247 AC: 3774 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3472

East Asian (EAS) AF: 0.600 AC: 3103 AN: 5172

South Asian (SAS) AF: 0.0188 AC: 91 AN: 4830

European-Finnish (FIN) AF: 0.0511 AC: 542 AN: 10600

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00349 AC: 237 AN: 67996

Other (OTH) AF: 0.0572 AC: 121 AN: 2116

Alfa AF: 0.0282 Hom.: 636

Bravo AF: 0.0719

Asia WGS AF: 0.197 AC: 681 AN: 3478

ClinVar

ClinVar submissions

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	-0.73
CADD	Benign	4.3
DANN	Benign	0.91
PhyloP100		-0.90
PromoterAI		0.010	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12488302; hg19: chr3-50341326;