Genetic Variant HS3ST3B1:c.-426T>C (chr17-14301093-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_006041.3(HS3ST3B1):c.-426T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 185,222 control chromosomes in the GnomAD database, including 5,346 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 0.23 ( 4320 hom., cov: 34)

Exomes 𝑓: 0.23 ( 1026 hom. )

Consequence

HS3ST3B1
NM_006041.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.578

Publications

6 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:

ENSG00000294706 (HGNC:):

ENSG00000294706 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS3ST3B1	NM_006041.3 link	c.-426T>C		5_prime_UTR_variant	Exon 1 of 2	ENST00000360954.3	NP_006032.1	Q9Y662
HS3ST3B1	NR_130138.2 link	n.13T>C		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
HS3ST3B1	ENST00000360954.3 link	c.-426T>C	5_prime_UTR_variant	Exon 1 of 2	1	NM_006041.3	ENSP00000354213.2	Q9Y662
HS3ST3B1	ENST00000466596.5 link	n.-426T>C	non_coding_transcript_exon_variant	Exon 1 of 3	2		ENSP00000436078.1	Q9Y662
ENSG00000294706	ENST00000725301.1 link	n.13A>G	non_coding_transcript_exon_variant	Exon 1 of 1
HS3ST3B1	ENST00000466596.5 link	n.-426T>C	5_prime_UTR_variant	Exon 1 of 3	2		ENSP00000436078.1	Q9Y662

Frequencies

GnomAD3 genomes

AF:

0.234

AC:

35558

AN:

152146

Hom.:

4323

Cov.:

show subpopulations

Gnomad AFR

AF:

0.205

Gnomad AMI

AF:

0.358

Gnomad AMR

AF:

0.228

Gnomad ASJ

AF:

0.308

Gnomad EAS

AF:

0.298

Gnomad SAS

AF:

0.416

Gnomad FIN

AF:

0.144

Gnomad MID

AF:

0.383

Gnomad NFE

AF:

0.241

Gnomad OTH

AF:

0.261

GnomAD4 exome

AF:

0.234

AC:

7712

AN:

32958

Hom.:

1026

Cov.:

AF XY:

0.240

AC XY:

3983

AN XY:

16576

show subpopulations

African (AFR)

AF:

0.237

AC:

263

AN:

1110

American (AMR)

AF:

0.235

AC:

180

AN:

766

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

358

AN:

1250

East Asian (EAS)

AF:

0.306

AC:

576

AN:

1880

South Asian (SAS)

AF:

0.327

AC:

390

AN:

1194

European-Finnish (FIN)

AF:

0.145

AC:

208

AN:

1430

Middle Eastern (MID)

AF:

0.320

AC:

AN:

172

European-Non Finnish (NFE)

AF:

0.226

AC:

5163

AN:

22860

Other (OTH)

AF:

0.226

AC:

519

AN:

2296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

267

533

800

1066

1333

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

150

200

250

<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:

0.234

AC:

35577

AN:

152264

Hom.:

4320

Cov.:

AF XY:

0.232

AC XY:

17303

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.205

AC:

8533

AN:

41572

American (AMR)

AF:

0.228

AC:

3491

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.308

AC:

1070

AN:

3472

East Asian (EAS)

AF:

0.298

AC:

1537

AN:

5156

South Asian (SAS)

AF:

0.415

AC:

2000

AN:

4822

European-Finnish (FIN)

AF:

0.144

AC:

1528

AN:

10610

Middle Eastern (MID)

AF:

0.371

AC:

109

AN:

294

European-Non Finnish (NFE)

AF:

0.241

AC:

16420

AN:

68014

Other (OTH)

AF:

0.266

AC:

563

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1437

2874

4312

5749

7186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

384

768

1152

1536

1920

<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:

0.237

Hom.:

12118

Bravo

AF:

0.238

Asia WGS

AF:

0.362

AC:

1260

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

0.58

PromoterAI

0.030

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=300/0

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