Genetic Variant HYAL3:p.Arg261Gln (chr3-50294821-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_003549.4(HYAL3):c.782G>A(p.Arg261Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000308 in 1,527,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

HYAL3
NM_003549.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.179

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.062915385).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HYAL3	NM_003549.4	MANE Select	c.782G>A	p.Arg261Gln	missense	Exon 2 of 4	NP_003540.2
HYAL3	NM_001200029.2		c.782G>A	p.Arg261Gln	missense	Exon 2 of 4	NP_001186958.1	O43820-1
HYAL3	NM_001200030.2		c.782G>A	p.Arg261Gln	missense	Exon 2 of 3	NP_001186959.1	O43820-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HYAL3	ENST00000336307.6	TSL:1 MANE Select	c.782G>A	p.Arg261Gln	missense	Exon 2 of 4	ENSP00000337425.1	O43820-1
HYAL3	ENST00000450982.6	TSL:1	c.782G>A	p.Arg261Gln	missense	Exon 2 of 3	ENSP00000391922.1	O43820-2
HYAL3	ENST00000415204.5	TSL:1	c.35G>A	p.Arg12Gln	missense	Exon 2 of 4	ENSP00000401092.1	O43820-3

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000526

AC:

AN:

190202

AF XY:

0.0000397

show subpopulations

Gnomad AFR exome

AF:

0.000321

Gnomad AMR exome

AF:

0.0000828

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000224

Gnomad OTH exome

AF:

0.000231

GnomAD4 exome

AF:

0.0000174

AC:

AN:

1375426

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

674106

show subpopulations

African (AFR)

AF:

0.000292

AC:

AN:

30776

American (AMR)

AF:

0.0000610

AC:

AN:

32790

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20452

East Asian (EAS)

AF:

0.00

AC:

AN:

38814

South Asian (SAS)

AF:

0.00

AC:

AN:

74376

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49766

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5326

European-Non Finnish (NFE)

AF:

0.00000375

AC:

AN:

1066702

Other (OTH)

AF:

0.000160

AC:

AN:

56424

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000151

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.000505

AC:

AN:

41582

American (AMR)

AF:

0.0000653

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.534

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000132

Hom.:

Bravo

AF:

0.000193

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000251

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.78

M_CAP

Benign

0.0086

MetaRNN

Benign

0.063

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

-0.18

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.074

Sift

Benign

0.13

Sift4G

Benign

0.19

Polyphen

0.83

Vest4

0.22

MVP

0.21

MPC

0.47

ClinPred

0.24

GERP RS

1.4

Varity_R

0.11

gMVP

0.71

Mutation Taster

=94/6

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over