17-14301718-G-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006041.3(HS3ST3B1):c.200G>C(p.Gly67Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000552 in 1,450,576 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G67V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

HS3ST3B1
NM_006041.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.45

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13085216).

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.200G>C	p.Gly67Ala	missense	Exon 1 of 2	NP_006032.1	Q9Y662
	HS3ST3B1	NR_130138.2		n.638G>C		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.200G>C	p.Gly67Ala	missense	Exon 1 of 2	ENSP00000354213.2	Q9Y662
	HS3ST3B1	ENST00000466596.5	TSL:2	n.200G>C		non_coding_transcript_exon	Exon 1 of 3	ENSP00000436078.1	Q9Y662

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000178

AC:

AN:

224216

AF XY:

0.0000160

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000534

Gnomad NFE exome

AF:

0.0000306

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000552

AC:

AN:

1450576

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

721326

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32644

American (AMR)

AF:

0.00

AC:

AN:

44118

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25750

East Asian (EAS)

AF:

0.00

AC:

AN:

39224

South Asian (SAS)

AF:

0.00

AC:

AN:

85702

European-Finnish (FIN)

AF:

0.0000611

AC:

AN:

49100

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5664

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1108512

Other (OTH)

AF:

0.0000501

AC:

AN:

59862

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

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

Cov.:

ExAC

AF:

0.0000343

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.0074

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.56

M_CAP

Pathogenic

0.34

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

PhyloP100

2.5

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.63

REVEL

Benign

0.089

Sift

Benign

0.13

Sift4G

Benign

0.20

Polyphen

0.0

Vest4

0.11

MutPred

0.26

Loss of loop (P = 0.0112)

MVP

0.48

ClinPred

0.092

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.069

gMVP

0.42

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over