chr17-13573086-T-C

Position:

• chr17-13573086-T-C

Variant summary

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

The NM_006042.3(HS3ST3A1):​c.599+27445A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 151,918 control chromosomes in the GnomAD database, including 13,766 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 (13766 hom., cov: 31)
• Consequence: HS3ST3A1 NM_006042.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.836

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HS3ST3A1	NM_006042.3	c.599+27445A>G		intron_variant		ENST00000284110.2	NP_006033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HS3ST3A1	ENST00000284110.2	c.599+27445A>G		intron_variant		1	NM_006042.3	ENSP00000284110	P1

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62049 AN: 151800 Hom.: 13744 Cov.: 31

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.409 AC: 62114 AN: 151918 Hom.: 13766 Cov.: 31 AF XY: 0.406 AC XY: 30153 AN XY: 74244

Gnomad4 AFR AF: 0.585

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.440

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.335

Gnomad4 OTH AF: 0.395

Alfa AF: 0.351 Hom.: 12750

Bravo AF: 0.415

Asia WGS AF: 0.496 AC: 1723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.96
DANN	Benign	0.79

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: rs3785692; hg19: chr17-13476403;