dbSNP rs9906590: HS3ST3B1:p.Glu363Lys (chr17-14345560-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_006041.3(HS3ST3B1):c.1087G>A(p.Glu363Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00275 in 1,585,204 control chromosomes in the GnomAD database, including 117 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 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 0.014 ( 69 hom., cov: 26)

Exomes 𝑓: 0.0015 ( 48 hom. )

Consequence

HS3ST3B1
NM_006041.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.01

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0044578016).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0144 (2192/151856) while in subpopulation AFR AF= 0.0498 (2065/41428). AF 95% confidence interval is 0.0481. There are 69 homozygotes in gnomad4. There are 1069 alleles in male gnomad4 subpopulation. Median coverage is 26. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 69 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS3ST3B1	NM_006041.3 link	c.1087G>A	p.Glu363Lys	missense_variant	Exon 2 of 2	ENST00000360954.3	NP_006032.1	Q9Y662
HS3ST3B1	XM_017025479.3 link	c.526G>A	p.Glu176Lys	missense_variant	Exon 2 of 2		XP_016880968.1
HS3ST3B1	NR_130138.2 link	n.1525G>A		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.1087G>A	p.Glu363Lys	missense_variant	Exon 2 of 2	1	NM_006041.3	ENSP00000354213.2		Q9Y662
HS3ST3B1	ENST00000466596.5 link	n.1087G>A		non_coding_transcript_exon_variant	Exon 2 of 3	2		ENSP00000436078.1		Q9Y662

Frequencies

GnomAD3 genomes

AF:

0.0144

AC:

2188

AN:

151740

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0499

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00505

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000417

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.0140

GnomAD3 exomes

AF:

0.00411

AC:

893

AN:

217402

Hom.:

AF XY:

0.00327

AC XY:

380

AN XY:

116154

show subpopulations

Gnomad AFR exome

AF:

0.0501

Gnomad AMR exome

AF:

0.00282

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000443

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000200

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.00151

AC:

2163

AN:

1433348

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

940

AN XY:

710890

show subpopulations

Gnomad4 AFR exome

AF:

0.0518

Gnomad4 AMR exome

AF:

0.00307

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000138

Gnomad4 FIN exome

AF:

0.0000191

Gnomad4 NFE exome

AF:

0.000101

Gnomad4 OTH exome

AF:

0.00347

GnomAD4 genome

AF:

0.0144

AC:

2192

AN:

151856

Hom.:

Cov.:

AF XY:

0.0144

AC XY:

1069

AN XY:

74212

show subpopulations

Gnomad4 AFR

AF:

0.0498

Gnomad4 AMR

AF:

0.00505

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000417

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.0138

Alfa

AF:

0.00598

Hom.:

Bravo

AF:

0.0166

ESP6500AA

AF:

0.0431

AC:

190

ESP6500EA

AF:

0.000351

AC:

ExAC

AF:

0.00444

AC:

539

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.85

MetaRNN

Benign

0.0045

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.2

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.8

REVEL

Benign

0.23

Sift

Benign

0.25

Sift4G

Benign

0.50

Polyphen

0.0010

Vest4

0.069

MVP

0.87

ClinPred

0.019

GERP RS

3.9

Varity_R

0.12

gMVP

0.52

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over