rs28663356

chr17-13601091-C-Achr17-13601091-C-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006042.3(HS3ST3A1):c.39G>T(p.Ser13=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 1,591,590 control chromosomes in the GnomAD database, including 556 homozygotes. 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: 𝑓 0.034 (241 hom., cov: 33)
  • Exomes 𝑓: 0.010 (315 hom.)
• Consequence: HS3ST3A1 NM_006042.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

Genes affected

HS3ST3A1 (HGNC:5196): (heparan sulfate-glucosamine 3-sulfotransferase 3A1) Heparan sulfate biosynthetic enzymes are key components in generating a myriad of distinct heparan sulfate fine structures that carry out multiple biologic activities. The enzyme encoded by this gene is a member of the heparan sulfate biosynthetic enzyme family. It is a type II integral membrane protein and possesses heparan sulfate glucosaminyl 3-O-sulfotransferase activity. The sulfotransferase domain of this enzyme is highly similar to the same domain of heparan sulfate D-glucosaminyl 3-O-sulfotransferase 3B1, and these two enzymes sulfate an identical disaccharide. This gene is widely expressed, with the most abundant expression in liver and placenta. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP7: Synonymous conserved (PhyloP=-1.43 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.098 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HS3ST3A1	NM_006042.3	c.39G>T	p.Ser13=	synonymous_variant	1/2	ENST00000284110.2
HS3ST3A1	XM_017025480.3	c.39G>T	p.Ser13=	synonymous_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HS3ST3A1	ENST00000284110.2	c.39G>T	p.Ser13=	synonymous_variant	1/2	1	NM_006042.3	P1

Frequencies

GnomAD3 genomes AF: 0.0337 AC: 5122 AN: 152138 Hom.: 238 Cov.: 33

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0175

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.0294

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.00566

Gnomad OTH AF: 0.0248

GnomAD3 exomes AF: 0.0160 AC: 3341 AN: 208742 Hom.: 97 AF XY: 0.0161 AC XY: 1830 AN XY: 113348

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.00857

Gnomad ASJ exome AF: 0.0265

Gnomad EAS exome AF: 0.0000662

Gnomad SAS exome AF: 0.0348

Gnomad FIN exome AF: 0.00157

Gnomad NFE exome AF: 0.00642

Gnomad OTH exome AF: 0.0125

GnomAD4 exome AF: 0.0102 AC: 14744 AN: 1439344 Hom.: 315 Cov.: 32 AF XY: 0.0107 AC XY: 7614 AN XY: 714416

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.00896

Gnomad4 ASJ exome AF: 0.0239

Gnomad4 EAS exome AF: 0.0000530

Gnomad4 SAS exome AF: 0.0340

Gnomad4 FIN exome AF: 0.00131

Gnomad4 NFE exome AF: 0.00594

Gnomad4 OTH exome AF: 0.0143

GnomAD4 genome AF: 0.0337 AC: 5136 AN: 152246 Hom.: 241 Cov.: 33 AF XY: 0.0336 AC XY: 2500 AN XY: 74440

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.0175

Gnomad4 ASJ AF: 0.0256

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0294

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.00568

Gnomad4 OTH AF: 0.0246

Alfa AF: 0.0136 Hom.: 29

Bravo AF: 0.0366

Asia WGS AF: 0.0160 AC: 56 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	0.92
Dann	Benign	0.71

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: rs28663356; hg19: chr17-13504408;