3-50293381-TC-AG

Variant names:

• chr3-50293381-TC-AG
• NM_003549.4:c.1118_1119delGAinsCT
• HYAL3 p.Gly373Ala

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_003549.4(HYAL3):​c.1118_1119delGAinsCT​(p.Gly373Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: HYAL3 NM_003549.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003549.4. 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
	HYAL3	NM_003549.4	MANE Select	c.1118_1119delGAinsCT	p.Gly373Ala	missense	N/A	NP_003540.2
	HYAL3	NM_001200029.2		c.1118_1119delGAinsCT	p.Gly373Ala	missense	N/A	NP_001186958.1	O43820-1
	HYAL3	NM_001200030.2		c.1028_1029delGAinsCT	p.Gly343Ala	missense	N/A	NP_001186959.1	O43820-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYAL3	ENST00000336307.6	TSL:1 MANE Select	c.1118_1119delGAinsCT	p.Gly373Ala	missense	N/A	ENSP00000337425.1	O43820-1
	HYAL3	ENST00000450982.6	TSL:1	c.1028_1029delGAinsCT	p.Gly343Ala	missense	N/A	ENSP00000391922.1	O43820-2
	HYAL3	ENST00000415204.5	TSL:1	c.371_372delGAinsCT	p.Gly124Ala	missense	N/A	ENSP00000401092.1	O43820-3

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.023

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-50330812;