Variant 17-14301851-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_006041.3(HS3ST3B1):c.333G>A(p.Pro111=) 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

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 -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 id 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HS3ST3B1	NM_006041.3 linkuse as main transcript	c.333G>A	p.Pro111=	synonymous_variant	1/2	ENST00000360954.3
HS3ST3B1	NR_130138.2 linkuse as main transcript	n.771G>A		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HS3ST3B1	ENST00000360954.3 linkuse as main transcript	c.333G>A	p.Pro111=	synonymous_variant	1/2	1	NM_006041.3	P1
HS3ST3B1	ENST00000466596.5 linkuse as main transcript	c.333G>A	p.Pro111=	synonymous_variant, NMD_transcript_variant	1/3	2

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

GnomAD3 exomes

AF:

0.00196

AC:

419

AN:

213692

Hom.:

AF XY:

0.00155

AC XY:

181

AN XY:

116462

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 SAS exome

AF:

0.000148

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

Gnomad4 AFR exome

AF:

0.0310

Gnomad4 AMR exome

AF:

0.00172

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000156

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000570

Gnomad4 OTH exome

AF:

0.00246

GnomAD4 genome

AF:

0.00843

AC:

1284

AN:

152318

Hom.:

Cov.:

AF XY:

0.00842

AC XY:

627

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0290

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00239

Hom.:

Bravo

AF:

0.00944

Asia WGS

AF:

0.00289

AC:

AN:

3478

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	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.8

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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