chr17-13601091-C-A

Variant names:

• chr17-13601091-C-A
• rs28663356
• NM_006042.3:c.39G>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006042.3(HS3ST3A1):​c.39G>T​(p.Ser13Ser) 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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006042.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST3A1	NM_006042.3	MANE Select	c.39G>T	p.Ser13Ser	synonymous	Exon 1 of 2	NP_006033.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST3A1	ENST00000284110.2	TSL:1 MANE Select	c.39G>T	p.Ser13Ser	synonymous	Exon 1 of 2	ENSP00000284110.1

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

GnomAD2 exomes AF: 0.0160 AC: 3341 AN: 208742 AF XY: 0.0161

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 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

African (AFR) AF: 0.104 AC: 3339 AN: 32150

American (AMR) AF: 0.00896 AC: 381 AN: 42510

Ashkenazi Jewish (ASJ) AF: 0.0239 AC: 607 AN: 25418

East Asian (EAS) AF: 0.0000530 AC: 2 AN: 37736

South Asian (SAS) AF: 0.0340 AC: 2816 AN: 82818

European-Finnish (FIN) AF: 0.00131 AC: 67 AN: 51094

Middle Eastern (MID) AF: 0.0230 AC: 131 AN: 5696

European-Non Finnish (NFE) AF: 0.00594 AC: 6553 AN: 1102542

Other (OTH) AF: 0.0143 AC: 848 AN: 59380

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

African (AFR) AF: 0.101 AC: 4177 AN: 41560

American (AMR) AF: 0.0175 AC: 268 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0256 AC: 89 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5142

South Asian (SAS) AF: 0.0294 AC: 142 AN: 4834

European-Finnish (FIN) AF: 0.00132 AC: 14 AN: 10620

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.00568 AC: 386 AN: 67996

Other (OTH) AF: 0.0246 AC: 52 AN: 2116

Alfa AF: 0.0141 Hom.: 30

Bravo AF: 0.0366

Asia WGS AF: 0.0160 AC: 56 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.92
DANN	Benign	0.71
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs28663356; hg19: chr17-13504408;