17-14301571-T-A

Position:

chr17-14301571-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006041.3(HS3ST3B1):c.53T>A(p.Leu18His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00212 in 1,595,528 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0033 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0020 ( 38 hom. )

Consequence

HS3ST3B1
NM_006041.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.20

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040172637).

BP6

Variant 17-14301571-T-A is Benign according to our data. Variant chr17-14301571-T-A is described in ClinVar as [Benign]. Clinvar id is 720013.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00334 (507/151686) while in subpopulation EAS AF= 0.0229 (117/5106). AF 95% confidence interval is 0.0195. There are 7 homozygotes in gnomad4. There are 265 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HS3ST3B1	NM_006041.3 link	c.53T>A	p.Leu18His	missense_variant	1/2	ENST00000360954.3	NP_006032.1	Q9Y662
HS3ST3B1	NR_130138.2 link	n.491T>A		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HS3ST3B1	ENST00000360954.3 link	c.53T>A	p.Leu18His	missense_variant	1/2	1	NM_006041.3	ENSP00000354213.2		Q9Y662
HS3ST3B1	ENST00000466596.5 link	n.53T>A		non_coding_transcript_exon_variant	1/3	2		ENSP00000436078.1		Q9Y662

Frequencies

GnomAD3 genomes

AF:

0.00335

AC:

508

AN:

151578

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000558

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0145

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0234

Gnomad SAS

AF:

0.000832

Gnomad FIN

AF:

0.00624

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00103

Gnomad OTH

AF:

0.00193

GnomAD3 exomes

AF:

0.00849

AC:

1816

AN:

213858

Hom.:

AF XY:

0.00699

AC XY:

837

AN XY:

119730

show subpopulations

Gnomad AFR exome

AF:

0.000510

Gnomad AMR exome

AF:

0.0354

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0242

Gnomad SAS exome

AF:

0.000102

Gnomad FIN exome

AF:

0.00694

Gnomad NFE exome

AF:

0.000993

Gnomad OTH exome

AF:

0.00653

GnomAD4 exome

AF:

0.00199

AC:

2877

AN:

1443842

Hom.:

Cov.:

AF XY:

0.00183

AC XY:

1315

AN XY:

718556

show subpopulations

Gnomad4 AFR exome

AF:

0.000305

Gnomad4 AMR exome

AF:

0.0321

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0125

Gnomad4 SAS exome

AF:

0.000152

Gnomad4 FIN exome

AF:

0.00701

Gnomad4 NFE exome

AF:

0.000428

Gnomad4 OTH exome

AF:

0.00297

GnomAD4 genome

AF:

0.00334

AC:

507

AN:

151686

Hom.:

Cov.:

AF XY:

0.00357

AC XY:

265

AN XY:

74150

show subpopulations

Gnomad4 AFR

AF:

0.000557

Gnomad4 AMR

AF:

0.0148

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0229

Gnomad4 SAS

AF:

0.000832

Gnomad4 FIN

AF:

0.00624

Gnomad4 NFE

AF:

0.00103

Gnomad4 OTH

AF:

0.000954

Alfa

AF:

0.00185

Hom.:

Bravo

AF:

0.00487

ESP6500AA

AF:

0.000539

AC:

ESP6500EA

AF:

0.000938

AC:

ExAC

AF:

0.00641

AC:

740

Asia WGS

AF:

0.00869

AC:

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0078

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.36

MetaRNN

Benign

0.0040

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.52

REVEL

Benign

0.081

Sift

Uncertain

0.0010

Sift4G

Benign

0.14

Polyphen

0.45

Vest4

0.39

MVP

0.27

ClinPred

0.042

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.12

gMVP

0.66

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over