rs62636622

chr17-14301851-G-Achr17-14301851-G-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.886

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]

ACMG classification

Verdict is Benign. Variant got -15 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_single_submitter, 1 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. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HS3ST3B1	NM_006041.3	c.333G>A	p.Pro111=	synonymous_variant	1/2	ENST00000360954.3
HS3ST3B1	NR_130138.2	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	c.333G>A	p.Pro111=	synonymous_variant	1/2	1	NM_006041.3	P1
HS3ST3B1	ENST00000466596.5	c.333G>A	p.Pro111=	synonymous_variant, NMD_transcript_variant	1/3	2

Frequencies

GnomAD3 genomes AF: 0.00840 AC: 1279 AN: 152200 Hom.: 23 Cov.: 33

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.: 3 AF XY: 0.00155 AC XY: 181 AN XY: 116462

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.: 19 Cov.: 31 AF XY: 0.000799 AC XY: 572 AN XY: 715974

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.: 23 Cov.: 33 AF XY: 0.00842 AC XY: 627 AN XY: 74492

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.: 5

Bravo AF: 0.00944

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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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

Other links and lift over

dbSNP: rs62636622; hg19: chr17-14205168;