rs12488302

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_153281.2(HYAL1):​c.-132G>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: HYAL1 NM_153281.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• 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: G2P, Ambry Genetics, Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYAL1	NM_153281.2	c.-132G>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 3 of 6		NP_695013.1
HYAL1	XM_011533668.3	c.-132G>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 4		XP_011531970.1
HYAL1	NM_153281.2	c.-132G>C		5_prime_UTR_variant	Exon 3 of 6		NP_695013.1
HYAL1	XM_011533668.3	c.-132G>C		5_prime_UTR_variant	Exon 1 of 4		XP_011531970.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HYAL1	ENST00000320295.12	c.-132G>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 3 of 6	2		ENSP00000346068.5
HYAL1	ENST00000618175.4	c.-132G>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 4	5		ENSP00000477903.1
HYAL1	ENST00000452672.1	c.-132G>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	4		ENSP00000391666.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 636

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.65
DANN	Benign	0.72
PhyloP100		-0.90
PromoterAI		-0.026	Neutral

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;