chr17-13555444-C-T

Variant names:

• chr17-13555444-C-T
• rs6502282
• NM_006042.3:c.599+45087G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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 -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.

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.599+45087G>A		intron	N/A	NP_006033.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST3A1	ENST00000284110.2	TSL:1 MANE Select	c.599+45087G>A		intron	N/A	ENSP00000284110.1
	HS3ST3A1	ENST00000578576.1	TSL:3	c.-8+499G>A		intron	N/A	ENSP00000462696.1

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

African (AFR) AF: 0.188 AC: 7813 AN: 41494

American (AMR) AF: 0.481 AC: 7352 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 1801 AN: 3468

East Asian (EAS) AF: 0.469 AC: 2412 AN: 5142

South Asian (SAS) AF: 0.510 AC: 2456 AN: 4820

European-Finnish (FIN) AF: 0.416 AC: 4379 AN: 10536

Middle Eastern (MID) AF: 0.524 AC: 153 AN: 292

European-Non Finnish (NFE) AF: 0.502 AC: 34108 AN: 67952

Other (OTH) AF: 0.447 AC: 945 AN: 2112

Alfa AF: 0.470 Hom.: 32699

Bravo AF: 0.402

Asia WGS AF: 0.438 AC: 1525 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.31
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6502282; hg19: chr17-13458761;