Genetic Variant HS3ST3B1:p.Pro211Pro (chr17-14345106-T-G) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_006041.3(HS3ST3B1):c.633T>G(p.Pro211Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 25)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HS3ST3B1
NM_006041.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.95

Publications

10 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP7

Synonymous conserved (PhyloP=-1.95 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
HS3ST3B1	NM_006041.3 link	c.633T>G	p.Pro211Pro	synonymous_variant	Exon 2 of 2	ENST00000360954.3	NP_006032.1
HS3ST3B1	XM_017025479.3 link	c.72T>G	p.Pro24Pro	synonymous_variant	Exon 2 of 2		XP_016880968.1
HS3ST3B1	NR_130138.2 link	n.1071T>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.633T>G	p.Pro211Pro	synonymous_variant	Exon 2 of 2	1	NM_006041.3	ENSP00000354213.2
HS3ST3B1	ENST00000466596.5 link	n.633T>G		non_coding_transcript_exon_variant	Exon 2 of 3	2		ENSP00000436078.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000549

AC:

AN:

182240

AF XY:

0.0000104

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:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000286

AC:

AN:

1399478

Hom.:

Cov.:

AF XY:

0.00000435

AC XY:

AN XY:

690126

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32924

American (AMR)

AF:

0.00

AC:

AN:

39034

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23382

East Asian (EAS)

AF:

0.00

AC:

AN:

38966

South Asian (SAS)

AF:

0.0000386

AC:

AN:

77810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50736

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5574

European-Non Finnish (NFE)

AF:

9.32e-7

AC:

AN:

1073130

Other (OTH)

AF:

0.00

AC:

AN:

57922

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

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.:

Alfa

AF:

0.00

Hom.:

3270

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

5.8

(source)

DANN

Benign

0.67

PhyloP100

-2.0

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over