rs28470223

chr17-13601706-A-G

Variant summary

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

The NM_006042.3(HS3ST3A1):c.-577T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 152,718 control chromosomes in the GnomAD database, including 13,480 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 0.38 (13457 hom., cov: 33)
  • Exomes 𝑓: 0.27 (23 hom.)
• Consequence: HS3ST3A1 NM_006042.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.73

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HS3ST3A1	NM_006042.3	c.-577T>C		5_prime_UTR_variant	1/2	ENST00000284110.2
HS3ST3A1	XM_017025480.3	c.-577T>C		5_prime_UTR_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HS3ST3A1	ENST00000284110.2	c.-577T>C		5_prime_UTR_variant	1/2	1	NM_006042.3	P1

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57935 AN: 152020 Hom.: 13431 Cov.: 33

Gnomad AFR AF: 0.659

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.0854

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.349

GnomAD4 exome AF: 0.269 AC: 156 AN: 580 Hom.: 23 Cov.: 0 AF XY: 0.261 AC XY: 106 AN XY: 406

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.125

Gnomad4 SAS exome AF: 0.438

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.263

Gnomad4 OTH exome AF: 0.182

GnomAD4 genome AF: 0.381 AC: 58009 AN: 152138 Hom.: 13457 Cov.: 33 AF XY: 0.371 AC XY: 27622 AN XY: 74372

Gnomad4 AFR AF: 0.659

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.0856

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.353

Alfa AF: 0.351 Hom.: 1382

Bravo AF: 0.396

Asia WGS AF: 0.228 AC: 793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.17
Dann	Benign	0.47

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: rs28470223; hg19: chr17-13505023;