17-13496169-AT-ATT

Position:

• chr17-13496169-AT-ATT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_006042.3(HS3ST3A1):​c.*27_*28insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,422,978 control chromosomes in the GnomAD database, including 53,840 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.38 (13079 hom., cov: 0)
  • Exomes 𝑓: 0.29 (40761 hom.)
• Consequence: HS3ST3A1 NM_006042.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.757

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HS3ST3A1	NM_006042.3	c.*27_*28insA		3_prime_UTR_variant	2/2	ENST00000284110.2	NP_006033.1
HS3ST3A1	XM_011524114.4	c.*27_*28insA		3_prime_UTR_variant	3/3		XP_011522416.1
HS3ST3A1	XM_047437228.1	c.*27_*28insA		3_prime_UTR_variant	2/2		XP_047293184.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HS3ST3A1	ENST00000284110.2	c.*27_*28insA		3_prime_UTR_variant	2/2	1	NM_006042.3	ENSP00000284110	P1
HS3ST3A1	ENST00000578576.1			downstream_gene_variant		3		ENSP00000462696

Frequencies

GnomAD3 genomes AF: 0.383 AC: 57762 AN: 150880 Hom.: 13059 Cov.: 0

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.397

GnomAD3 exomes AF: 0.320 AC: 49649 AN: 155092 Hom.: 5868 AF XY: 0.318 AC XY: 27120 AN XY: 85292

Gnomad AFR exome AF: 0.621

Gnomad AMR exome AF: 0.299

Gnomad ASJ exome AF: 0.359

Gnomad EAS exome AF: 0.214

Gnomad SAS exome AF: 0.300

Gnomad FIN exome AF: 0.253

Gnomad NFE exome AF: 0.316

Gnomad OTH exome AF: 0.332

GnomAD4 exome AF: 0.290 AC: 369420 AN: 1271994 Hom.: 40761 Cov.: 35 AF XY: 0.289 AC XY: 181266 AN XY: 626856

Gnomad4 AFR exome AF: 0.615

Gnomad4 AMR exome AF: 0.278

Gnomad4 ASJ exome AF: 0.342

Gnomad4 EAS exome AF: 0.202

Gnomad4 SAS exome AF: 0.271

Gnomad4 FIN exome AF: 0.240

Gnomad4 NFE exome AF: 0.286

Gnomad4 OTH exome AF: 0.311

GnomAD4 genome AF: 0.383 AC: 57826 AN: 150984 Hom.: 13079 Cov.: 0 AF XY: 0.374 AC XY: 27543 AN XY: 73708

Gnomad4 AFR AF: 0.648

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.338

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.396

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs67951062; hg19: chr17-13399486;