rs8080565

Positions:

• chr17-13496836-G-A
• chr17-13496836-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006042.3(HS3ST3A1):​c.600-18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0644 in 1,606,328 control chromosomes in the GnomAD database, including 3,558 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 0.067 (384 hom., cov: 30)
  • Exomes 𝑓: 0.064 (3174 hom.)
• Consequence: HS3ST3A1 NM_006042.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.602

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HS3ST3A1	NM_006042.3	c.600-18C>T		intron_variant		ENST00000284110.2	NP_006033.1
HS3ST3A1	XM_011524114.4	c.3-18C>T		intron_variant			XP_011522416.1
HS3ST3A1	XM_047437228.1	c.3-18C>T		intron_variant			XP_047293184.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HS3ST3A1	ENST00000284110.2	c.600-18C>T		intron_variant		1	NM_006042.3	ENSP00000284110	P1
HS3ST3A1	ENST00000578576.1	c.-7-18C>T		intron_variant		3		ENSP00000462696

Frequencies

GnomAD3 genomes AF: 0.0671 AC: 10200 AN: 151986 Hom.: 384 Cov.: 30

Gnomad AFR AF: 0.0879

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0440

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.00291

Gnomad SAS AF: 0.0247

Gnomad FIN AF: 0.0545

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0710

Gnomad OTH AF: 0.0694

GnomAD3 exomes AF: 0.0533 AC: 13075 AN: 245092 Hom.: 424 AF XY: 0.0533 AC XY: 7049 AN XY: 132146

Gnomad AFR exome AF: 0.0887

Gnomad AMR exome AF: 0.0290

Gnomad ASJ exome AF: 0.0486

Gnomad EAS exome AF: 0.00114

Gnomad SAS exome AF: 0.0292

Gnomad FIN exome AF: 0.0548

Gnomad NFE exome AF: 0.0708

Gnomad OTH exome AF: 0.0527

GnomAD4 exome AF: 0.0641 AC: 93167 AN: 1454224 Hom.: 3174 Cov.: 33 AF XY: 0.0630 AC XY: 45498 AN XY: 722584

Gnomad4 AFR exome AF: 0.0924

Gnomad4 AMR exome AF: 0.0306

Gnomad4 ASJ exome AF: 0.0473

Gnomad4 EAS exome AF: 0.00136

Gnomad4 SAS exome AF: 0.0292

Gnomad4 FIN exome AF: 0.0579

Gnomad4 NFE exome AF: 0.0706

Gnomad4 OTH exome AF: 0.0570

GnomAD4 genome AF: 0.0671 AC: 10206 AN: 152104 Hom.: 384 Cov.: 30 AF XY: 0.0645 AC XY: 4799 AN XY: 74346

Gnomad4 AFR AF: 0.0878

Gnomad4 AMR AF: 0.0439

Gnomad4 ASJ AF: 0.0444

Gnomad4 EAS AF: 0.00292

Gnomad4 SAS AF: 0.0249

Gnomad4 FIN AF: 0.0545

Gnomad4 NFE AF: 0.0710

Gnomad4 OTH AF: 0.0691

Alfa AF: 0.0631 Hom.: 487

Bravo AF: 0.0682

Asia WGS AF: 0.0260 AC: 92 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.53
DANN	Benign	0.81

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: rs8080565; hg19: chr17-13400153;