NM_006041.3:c.333G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_006041.3(HS3ST3B1):c.333G>A(p.Pro111Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,595,602 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0084 ( 23 hom., cov: 33)

Exomes 𝑓: 0.00093 ( 19 hom. )

Consequence

HS3ST3B1
NM_006041.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.886

Publications

3 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 17-14301851-G-A is Benign according to our data. Variant chr17-14301851-G-A is described in ClinVar as Benign. ClinVar VariationId is 708974.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.886 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00843 (1284/152318) while in subpopulation AFR AF = 0.029 (1204/41572). AF 95% confidence interval is 0.0276. There are 23 homozygotes in GnomAd4. There are 627 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 23 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006041.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST3B1	NM_006041.3	MANE Select	c.333G>A	p.Pro111Pro	synonymous	Exon 1 of 2	NP_006032.1	Q9Y662
	HS3ST3B1	NR_130138.2		n.771G>A		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST3B1	ENST00000360954.3	TSL:1 MANE Select	c.333G>A	p.Pro111Pro	synonymous	Exon 1 of 2	ENSP00000354213.2	Q9Y662
	HS3ST3B1	ENST00000466596.5	TSL:2	n.333G>A		non_coding_transcript_exon	Exon 1 of 3	ENSP00000436078.1	Q9Y662

Frequencies

GnomAD3 genomes

AF:

0.00840

AC:

1279

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00379

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00717

GnomAD2 exomes

AF:

0.00196

AC:

419

AN:

213692

AF XY:

0.00155

show subpopulations

Gnomad AFR exome

AF:

0.0291

Gnomad AMR exome

AF:

0.00168

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000636

Gnomad OTH exome

AF:

0.000939

GnomAD4 exome

AF:

0.000926

AC:

1336

AN:

1443284

Hom.:

Cov.:

AF XY:

0.000799

AC XY:

572

AN XY:

715974

show subpopulations

African (AFR)

AF:

0.0310

AC:

1031

AN:

33298

American (AMR)

AF:

0.00172

AC:

AN:

41750

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25606

East Asian (EAS)

AF:

0.00

AC:

AN:

38996

South Asian (SAS)

AF:

0.000156

AC:

AN:

83084

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50816

Middle Eastern (MID)

AF:

0.00177

AC:

AN:

5636

European-Non Finnish (NFE)

AF:

0.0000570

AC:

AN:

1104396

Other (OTH)

AF:

0.00246

AC:

147

AN:

59702

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

177

266

354

443

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<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:

0.00843

AC:

1284

AN:

152318

Hom.:

Cov.:

AF XY:

0.00842

AC XY:

627

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.0290

AC:

1204

AN:

41572

American (AMR)

AF:

0.00379

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68032

Other (OTH)

AF:

0.00710

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

127

190

254

317

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00239

Hom.:

Bravo

AF:

0.00944

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.8

(source)

DANN

Benign

0.87

PhyloP100

-0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Mutation Taster

=100/0

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

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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