Genetic Variant HS3ST3A1:c.-28G>A (chr17-13601157-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006042.3(HS3ST3A1):c.-28G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,478,940 control chromosomes in the GnomAD database, including 9,361 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 0.12 ( 1134 hom., cov: 33)

Exomes 𝑓: 0.11 ( 8227 hom. )

Consequence

HS3ST3A1
NM_006042.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.531

Variant links:

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]

HS3ST3A1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS3ST3A1	NM_006042.3 link	c.-28G>A		5_prime_UTR_variant	Exon 1 of 2	ENST00000284110.2	NP_006033.1	Q9Y663
HS3ST3A1	XM_017025480.3 link	c.-28G>A		5_prime_UTR_variant	Exon 1 of 2		XP_016880969.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HS3ST3A1	ENST00000284110.2 link	c.-28G>A		5_prime_UTR_variant	Exon 1 of 2	1	NM_006042.3	ENSP00000284110.1		Q9Y663

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

17901

AN:

152140

Hom.:

1134

Cov.:

show subpopulations

Gnomad AFR

AF:

0.162

Gnomad AMI

AF:

0.241

Gnomad AMR

AF:

0.0850

Gnomad ASJ

AF:

0.110

Gnomad EAS

AF:

0.0152

Gnomad SAS

AF:

0.0897

Gnomad FIN

AF:

0.0727

Gnomad MID

AF:

0.159

Gnomad NFE

AF:

0.113

Gnomad OTH

AF:

0.116

GnomAD3 exomes

AF:

0.0965

AC:

8618

AN:

89328

Hom.:

466

AF XY:

0.0972

AC XY:

4501

AN XY:

46286

show subpopulations

Gnomad AFR exome

AF:

0.167

Gnomad AMR exome

AF:

0.0582

Gnomad ASJ exome

AF:

0.133

Gnomad EAS exome

AF:

0.0143

Gnomad SAS exome

AF:

0.0926

Gnomad FIN exome

AF:

0.0756

Gnomad NFE exome

AF:

0.122

Gnomad OTH exome

AF:

0.110

GnomAD4 exome

AF:

0.108

AC:

143477

AN:

1326686

Hom.:

8227

Cov.:

AF XY:

0.108

AC XY:

70096

AN XY:

651308

show subpopulations

Gnomad4 AFR exome

AF:

0.170

Gnomad4 AMR exome

AF:

0.0636

Gnomad4 ASJ exome

AF:

0.118

Gnomad4 EAS exome

AF:

0.0379

Gnomad4 SAS exome

AF:

0.0898

Gnomad4 FIN exome

AF:

0.0757

Gnomad4 NFE exome

AF:

0.112

Gnomad4 OTH exome

AF:

0.109

GnomAD4 genome

AF:

0.118

AC:

17916

AN:

152254

Hom.:

1134

Cov.:

AF XY:

0.113

AC XY:

8386

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.162

Gnomad4 AMR

AF:

0.0848

Gnomad4 ASJ

AF:

0.110

Gnomad4 EAS

AF:

0.0153

Gnomad4 SAS

AF:

0.0902

Gnomad4 FIN

AF:

0.0727

Gnomad4 NFE

AF:

0.113

Gnomad4 OTH

AF:

0.118

Alfa

AF:

0.0739

Hom.:

149

Bravo

AF:

0.121

Asia WGS

AF:

0.0580

AC:

204

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.95

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over