rs6502282

Positions:

• chr17-13555444-C-T

Variant summary

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

The NM_006042.3(HS3ST3A1):​c.599+45087G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 151,994 control chromosomes in the GnomAD database, including 14,036 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 0.41 (14036 hom., cov: 32)
• Consequence: HS3ST3A1 NM_006042.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HS3ST3A1	NM_006042.3	c.599+45087G>A		intron_variant		ENST00000284110.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HS3ST3A1	ENST00000284110.2	c.599+45087G>A		intron_variant		1	NM_006042.3	P1
HS3ST3A1	ENST00000578576.1	c.-8+499G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61957 AN: 151876 Hom.: 14046 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.451

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.408 AC: 61956 AN: 151994 Hom.: 14036 Cov.: 32 AF XY: 0.410 AC XY: 30425 AN XY: 74268

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.481

Gnomad4 ASJ AF: 0.519

Gnomad4 EAS AF: 0.469

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.416

Gnomad4 NFE AF: 0.502

Gnomad4 OTH AF: 0.447

Alfa AF: 0.484 Hom.: 9012

Bravo AF: 0.402

Asia WGS AF: 0.438 AC: 1525 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs6502282; hg19: chr17-13458761;