rs62056073

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_006041.3(HS3ST3B1):c.586A>G(p.Ile196Val) variant causes a missense change. The variant allele was found at a frequency of 0.0243 in 1,587,252 control chromosomes in the GnomAD database, including 566 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 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 0.017 ( 33 hom., cov: 31)

Exomes 𝑓: 0.025 ( 533 hom. )

Consequence

HS3ST3B1
NM_006041.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.01

Publications

7 publications found

Variant links:

Genes affected

HS3ST3B1 (HGNC:5198): (heparan sulfate-glucosamine 3-sulfotransferase 3B1) The protein encoded by this gene is a type II integral membrane protein that belongs to the 3-O-sulfotransferases family. These proteins catalyze the addition of sulfate groups at the 3-OH position of glucosamine in heparan sulfate. The substrate specificity of individual members of the family is based on prior modification of the heparan sulfate chain, thus allowing different members of the family to generate binding sites for different proteins on the same heparan sulfate chain. Following treatment with a histone deacetylase inhibitor, expression of this gene is activated in a pancreatic cell line. The increased expression results in promotion of the epithelial-mesenchymal transition. In addition, the modification catalyzed by this protein allows herpes simplex virus membrane fusion and penetration. A very closely related homolog with an almost identical sulfotransferase domain maps less than 1 Mb away. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

HS3ST3B1 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 (MetaRNN=0.006789446).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0171 (2599/152150) while in subpopulation SAS AF = 0.0428 (206/4818). AF 95% confidence interval is 0.038. There are 33 homozygotes in GnomAd4. There are 1268 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS3ST3B1	NM_006041.3 link	c.586A>G	p.Ile196Val	missense_variant	Exon 2 of 2	ENST00000360954.3	NP_006032.1	Q9Y662
HS3ST3B1	XM_017025479.3 link	c.25A>G	p.Ile9Val	missense_variant	Exon 2 of 2		XP_016880968.1
HS3ST3B1	NR_130138.2 link	n.1024A>G		non_coding_transcript_exon_variant	Exon 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HS3ST3B1	ENST00000360954.3 link	c.586A>G	p.Ile196Val	missense_variant	Exon 2 of 2	1	NM_006041.3	ENSP00000354213.2		Q9Y662
HS3ST3B1	ENST00000466596.5 link	n.586A>G		non_coding_transcript_exon_variant	Exon 2 of 3	2		ENSP00000436078.1		Q9Y662

Frequencies

GnomAD3 genomes

AF:

0.0171

AC:

2599

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00529

Gnomad AMI

AF:

0.00440

Gnomad AMR

AF:

0.0164

Gnomad ASJ

AF:

0.0251

Gnomad EAS

AF:

0.000581

Gnomad SAS

AF:

0.0423

Gnomad FIN

AF:

0.0131

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0242

Gnomad OTH

AF:

0.0191

GnomAD2 exomes

AF:

0.0202

AC:

4682

AN:

231756

AF XY:

0.0222

show subpopulations

Gnomad AFR exome

AF:

0.00358

Gnomad AMR exome

AF:

0.0128

Gnomad ASJ exome

AF:

0.0249

Gnomad EAS exome

AF:

0.000169

Gnomad FIN exome

AF:

0.0127

Gnomad NFE exome

AF:

0.0240

Gnomad OTH exome

AF:

0.0273

GnomAD4 exome

AF:

0.0251

AC:

36020

AN:

1435102

Hom.:

533

Cov.:

AF XY:

0.0258

AC XY:

18359

AN XY:

711168

show subpopulations

African (AFR)

AF:

0.00391

AC:

130

AN:

33286

American (AMR)

AF:

0.0131

AC:

548

AN:

41784

Ashkenazi Jewish (ASJ)

AF:

0.0265

AC:

647

AN:

24394

East Asian (EAS)

AF:

0.000126

AC:

AN:

39540

South Asian (SAS)

AF:

0.0426

AC:

3476

AN:

81658

European-Finnish (FIN)

AF:

0.0124

AC:

645

AN:

52142

Middle Eastern (MID)

AF:

0.0269

AC:

152

AN:

5644

European-Non Finnish (NFE)

AF:

0.0263

AC:

28899

AN:

1097406

Other (OTH)

AF:

0.0256

AC:

1518

AN:

59248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

1617

3235

4852

6470

8087

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1130

2260

3390

4520

5650

<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:

0.0171

AC:

2599

AN:

152150

Hom.:

Cov.:

AF XY:

0.0171

AC XY:

1268

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.00527

AC:

219

AN:

41540

American (AMR)

AF:

0.0164

AC:

250

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0251

AC:

AN:

3472

East Asian (EAS)

AF:

0.000583

AC:

AN:

5150

South Asian (SAS)

AF:

0.0428

AC:

206

AN:

4818

European-Finnish (FIN)

AF:

0.0131

AC:

139

AN:

10594

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0242

AC:

1646

AN:

67984

Other (OTH)

AF:

0.0189

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

120

240

361

481

601

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.0206

Hom.:

Bravo

AF:

0.0162

TwinsUK

AF:

0.0340

AC:

126

ALSPAC

AF:

0.0265

AC:

102

ESP6500AA

AF:

0.00431

AC:

ESP6500EA

AF:

0.0271

AC:

233

ExAC

AF:

0.0217

AC:

2630

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

Eigen

Benign

-0.10

Eigen_PC

Benign

0.018

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.92

MetaRNN

Benign

0.0068

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

5.0

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.92

REVEL

Benign

0.068

Sift

Benign

0.065

Sift4G

Benign

0.099

Polyphen

0.040

Vest4

0.054

ClinPred

0.035

GERP RS

3.5

Varity_R

0.13

gMVP

0.48

Mutation Taster

=94/6

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over