Genetic Variant HYAL3:c.985-41A>G (chr3-50293556-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003549.4(HYAL3):c.985-41A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0431 in 1,611,666 control chromosomes in the GnomAD database, including 12,981 homozygotes. 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: 𝑓 0.10 ( 2267 hom., cov: 33)

Exomes 𝑓: 0.037 ( 10714 hom. )

Consequence

HYAL3
NM_003549.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.260

Publications

6 publications found

Variant links:

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]

HYAL3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYAL3	NM_003549.4 link	c.985-41A>G		intron_variant	Intron 3 of 3	ENST00000336307.6	NP_003540.2	O43820-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HYAL3	ENST00000336307.6 link	c.985-41A>G		intron_variant	Intron 3 of 3	1	NM_003549.4	ENSP00000337425.1		O43820-1

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

15713

AN:

152142

Hom.:

2265

Cov.:

show subpopulations

Gnomad AFR

AF:

0.181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.266

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.599

Gnomad SAS

AF:

0.0211

Gnomad FIN

AF:

0.0468

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00359

Gnomad OTH

AF:

0.0865

GnomAD2 exomes

AF:

0.122

AC:

30393

AN:

250048

AF XY:

0.0990

show subpopulations

Gnomad AFR exome

AF:

0.177

Gnomad AMR exome

AF:

0.412

Gnomad ASJ exome

AF:

0.00332

Gnomad EAS exome

AF:

0.614

Gnomad FIN exome

AF:

0.0446

Gnomad NFE exome

AF:

0.00352

Gnomad OTH exome

AF:

0.0676

GnomAD4 exome

AF:

0.0368

AC:

53716

AN:

1459406

Hom.:

10714

Cov.:

AF XY:

0.0333

AC XY:

24171

AN XY:

725636

show subpopulations

African (AFR)

AF:

0.193

AC:

6466

AN:

33428

American (AMR)

AF:

0.389

AC:

17367

AN:

44620

Ashkenazi Jewish (ASJ)

AF:

0.00426

AC:

111

AN:

26054

East Asian (EAS)

AF:

0.535

AC:

21186

AN:

39606

South Asian (SAS)

AF:

0.0102

AC:

880

AN:

86206

European-Finnish (FIN)

AF:

0.0440

AC:

2335

AN:

53022

Middle Eastern (MID)

AF:

0.00729

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00173

AC:

1920

AN:

1110420

Other (OTH)

AF:

0.0565

AC:

3409

AN:

60292

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

2149

4297

6446

8594

10743

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

708

1416

2124

2832

3540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.103

AC:

15743

AN:

152260

Hom.:

2267

Cov.:

AF XY:

0.110

AC XY:

8185

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.181

AC:

7527

AN:

41532

American (AMR)

AF:

0.266

AC:

4076

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00461

AC:

AN:

3472

East Asian (EAS)

AF:

0.599

AC:

3096

AN:

5166

South Asian (SAS)

AF:

0.0209

AC:

101

AN:

4832

European-Finnish (FIN)

AF:

0.0468

AC:

497

AN:

10622

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00359

AC:

244

AN:

68016

Other (OTH)

AF:

0.0870

AC:

184

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

594

1187

1781

2374

2968

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

146

292

438

584

730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0640

Hom.:

497

Bravo

AF:

0.129

Asia WGS

AF:

0.206

AC:

713

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.63

(source)

DANN

Benign

0.41

PhyloP100

-0.26

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over