rs201721482

Variant names:

• chr17-14301551-C-T
• rs201721482
• NM_006041.3:c.33C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_006041.3(HS3ST3B1):​c.33C>T​(p.Cys11Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00284 in 1,584,494 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0030 (15 hom.)
• Consequence: HS3ST3B1 NM_006041.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.672
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 17-14301551-C-T is Benign according to our data. Variant chr17-14301551-C-T is described in ClinVar as Benign. ClinVar VariationId is 774514.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.672 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 15 AR gene

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.33C>T	p.Cys11Cys	synonymous	Exon 1 of 2	NP_006032.1	Q9Y662
	HS3ST3B1	NR_130138.2		n.471C>T		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.33C>T	p.Cys11Cys	synonymous	Exon 1 of 2	ENSP00000354213.2	Q9Y662
	HS3ST3B1	ENST00000466596.5	TSL:2	n.33C>T		non_coding_transcript_exon	Exon 1 of 3	ENSP00000436078.1	Q9Y662

Frequencies

GnomAD3 genomes AF: 0.00175 AC: 266 AN: 152058 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000848

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00327

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.00150 AC: 295 AN: 197098 AF XY: 0.00148

Gnomad AFR exome AF: 0.000283

Gnomad AMR exome AF: 0.000800

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000839

Gnomad NFE exome AF: 0.00277

Gnomad OTH exome AF: 0.00338

GnomAD4 exome AF: 0.00296 AC: 4238 AN: 1432328 Hom.: 15 Cov.: 31 AF XY: 0.00283 AC XY: 2016 AN XY: 712152

African (AFR) AF: 0.000369 AC: 12 AN: 32520

American (AMR) AF: 0.000708 AC: 30 AN: 42398

Ashkenazi Jewish (ASJ) AF: 0.0000783 AC: 2 AN: 25528

East Asian (EAS) AF: 0.00 AC: 0 AN: 38914

South Asian (SAS) AF: 0.00 AC: 0 AN: 84350

European-Finnish (FIN) AF: 0.000656 AC: 25 AN: 38106

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5686

European-Non Finnish (NFE) AF: 0.00363 AC: 4009 AN: 1105278

Other (OTH) AF: 0.00267 AC: 159 AN: 59548

GnomAD4 genome AF: 0.00174 AC: 265 AN: 152166 Hom.: 0 Cov.: 33 AF XY: 0.00161 AC XY: 120 AN XY: 74384

African (AFR) AF: 0.000481 AC: 20 AN: 41546

American (AMR) AF: 0.000850 AC: 13 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5132

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.000848 AC: 9 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00325 AC: 221 AN: 67978

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.00223 Hom.: 0

Bravo AF: 0.00188

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	14
DANN	Uncertain	0.98
PhyloP100		0.67
PromoterAI		0.12	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs201721482; hg19: chr17-14204868;