17-13496299-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006042.3(HS3ST3A1):c.1119T>A(p.Pro373=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 1,529,094 control chromosomes in the GnomAD database, including 91,013 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 0.33 (8532 hom., cov: 27)
  • Exomes 𝑓: 0.36 (82481 hom.)
• Consequence: HS3ST3A1 NM_006042.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=-0.454 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HS3ST3A1	NM_006042.3	c.1119T>A	p.Pro373=	synonymous_variant	2/2	ENST00000284110.2
HS3ST3A1	XM_011524114.4	c.522T>A	p.Pro174=	synonymous_variant	3/3
HS3ST3A1	XM_047437228.1	c.522T>A	p.Pro174=	synonymous_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HS3ST3A1	ENST00000284110.2	c.1119T>A	p.Pro373=	synonymous_variant	2/2	1	NM_006042.3	P1
HS3ST3A1	ENST00000578576.1	c.513T>A	p.Pro171=	synonymous_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.332 AC: 49246 AN: 148452 Hom.: 8521 Cov.: 27

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.352

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.330

GnomAD3 exomes AF: 0.385 AC: 78269 AN: 203314 Hom.: 15618 AF XY: 0.387 AC XY: 42813 AN XY: 110748

Gnomad AFR exome AF: 0.208

Gnomad AMR exome AF: 0.563

Gnomad ASJ exome AF: 0.315

Gnomad EAS exome AF: 0.512

Gnomad SAS exome AF: 0.545

Gnomad FIN exome AF: 0.269

Gnomad NFE exome AF: 0.344

Gnomad OTH exome AF: 0.360

GnomAD4 exome AF: 0.363 AC: 501192 AN: 1380528 Hom.: 82481 Cov.: 29 AF XY: 0.365 AC XY: 250051 AN XY: 684314

Gnomad4 AFR exome AF: 0.203

Gnomad4 AMR exome AF: 0.536

Gnomad4 ASJ exome AF: 0.327

Gnomad4 EAS exome AF: 0.518

Gnomad4 SAS exome AF: 0.491

Gnomad4 FIN exome AF: 0.270

Gnomad4 NFE exome AF: 0.353

Gnomad4 OTH exome AF: 0.368

GnomAD4 genome AF: 0.332 AC: 49294 AN: 148566 Hom.: 8532 Cov.: 27 AF XY: 0.338 AC XY: 24487 AN XY: 72342

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.492

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.531

Gnomad4 SAS AF: 0.550

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.333

Alfa AF: 0.229 Hom.: 683

Bravo AF: 0.347

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	1.1
Dann	Benign	0.78

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: rs61741326; hg19: chr17-13399616; COSMIC: COSV52375136;