rs13100173

Variant names:

• chr3-50295266-G-A
• rs13100173
• NM_003549.4:c.337C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000336307.6(HYAL3):​c.337C>T​(p.His113Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 1,613,800 control chromosomes in the GnomAD database, including 157,583 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.35 (11198 hom., cov: 34)
  • Exomes 𝑓: 0.44 (146385 hom.)
• Consequence: HYAL3 ENST00000336307.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.447
• Publications: 75 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.1286478E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000336307.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYAL3	NM_003549.4	MANE Select	c.337C>T	p.His113Tyr	missense	Exon 2 of 4	NP_003540.2
	HYAL3	NM_001200029.2		c.337C>T	p.His113Tyr	missense	Exon 2 of 4	NP_001186958.1
	HYAL3	NM_001200030.2		c.337C>T	p.His113Tyr	missense	Exon 2 of 3	NP_001186959.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYAL3	ENST00000336307.6	TSL:1 MANE Select	c.337C>T	p.His113Tyr	missense	Exon 2 of 4	ENSP00000337425.1
	HYAL3	ENST00000450982.6	TSL:1	c.337C>T	p.His113Tyr	missense	Exon 2 of 3	ENSP00000391922.1
	HYAL3	ENST00000415204.5	TSL:1	c.3-413C>T		intron	N/A	ENSP00000401092.1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53554 AN: 152144 Hom.: 11191 Cov.: 34

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.0908

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.392

GnomAD2 exomes AF: 0.369 AC: 92728 AN: 251198 AF XY: 0.374

Gnomad AFR exome AF: 0.151

Gnomad AMR exome AF: 0.304

Gnomad ASJ exome AF: 0.422

Gnomad EAS exome AF: 0.0901

Gnomad FIN exome AF: 0.424

Gnomad NFE exome AF: 0.478

Gnomad OTH exome AF: 0.407

GnomAD4 exome AF: 0.437 AC: 638924 AN: 1461536 Hom.: 146385 Cov.: 61 AF XY: 0.433 AC XY: 315036 AN XY: 727090

African (AFR) AF: 0.142 AC: 4738 AN: 33478

American (AMR) AF: 0.311 AC: 13917 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 11056 AN: 26134

East Asian (EAS) AF: 0.130 AC: 5144 AN: 39700

South Asian (SAS) AF: 0.257 AC: 22201 AN: 86258

European-Finnish (FIN) AF: 0.423 AC: 22503 AN: 53148

Middle Eastern (MID) AF: 0.372 AC: 2147 AN: 5768

European-Non Finnish (NFE) AF: 0.479 AC: 532763 AN: 1111940

Other (OTH) AF: 0.405 AC: 24455 AN: 60390

GnomAD4 genome AF: 0.352 AC: 53562 AN: 152264 Hom.: 11198 Cov.: 34 AF XY: 0.345 AC XY: 25714 AN XY: 74436

African (AFR) AF: 0.159 AC: 6595 AN: 41572

American (AMR) AF: 0.366 AC: 5597 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1513 AN: 3470

East Asian (EAS) AF: 0.0903 AC: 468 AN: 5180

South Asian (SAS) AF: 0.241 AC: 1163 AN: 4826

European-Finnish (FIN) AF: 0.426 AC: 4514 AN: 10588

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.476 AC: 32369 AN: 68000

Other (OTH) AF: 0.393 AC: 832 AN: 2116

Alfa AF: 0.426 Hom.: 39320

Bravo AF: 0.341

TwinsUK AF: 0.474 AC: 1758

ALSPAC AF: 0.490 AC: 1887

ESP6500AA AF: 0.165 AC: 727

ESP6500EA AF: 0.484 AC: 4163

ExAC AF: 0.369 AC: 44756

Asia WGS AF: 0.212 AC: 742 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	12
DANN	Benign	0.83
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.34	T
MetaRNN	Benign	0.00031	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.45
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.036
Sift	Benign	0.29	T
Sift4G	Benign	0.32	T
Polyphen		0.30	B
Vest4		0.10
MPC		0.66
ClinPred		0.0066	T
GERP RS		1.6
Varity_R		0.098
gMVP		0.50
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: rs13100173; hg19: chr3-50332697; COSMIC: COSV56497193; COSMIC: COSV56497193;