Genetic Variant HS3ST3A1:c.*26_*27dupAA (chr17-13496169-A-ATT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_006042.3(HS3ST3A1):c.*26_*27dupAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,439,400 control chromosomes in the GnomAD database, including 64,625 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.36 ( 10664 hom., cov: 0)

Exomes 𝑓: 0.36 ( 53961 hom. )

Consequence

HS3ST3A1
NM_006042.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.757

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 was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
HS3ST3A1	NM_006042.3 link	c.26_27dupAA	3_prime_UTR_variant	Exon 2 of 2	ENST00000284110.2	NP_006033.1	Q9Y663
HS3ST3A1	XM_011524114.4 link	c.26_27dupAA	3_prime_UTR_variant	Exon 3 of 3		XP_011522416.1
HS3ST3A1	XM_047437228.1 link	c.26_27dupAA	3_prime_UTR_variant	Exon 2 of 2		XP_047293184.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
HS3ST3A1	ENST00000284110 link	c.26_27dupAA	3_prime_UTR_variant	Exon 2 of 2	1	NM_006042.3	ENSP00000284110.1	Q9Y663
HS3ST3A1	ENST00000578576.1 link	c.26_27dupAA	splice_region_variant	Exon 2 of 2	3		ENSP00000462696.1	J3KSX5
HS3ST3A1	ENST00000578576 link	c.26_27dupAA	3_prime_UTR_variant	Exon 2 of 2	3		ENSP00000462696.1	J3KSX5

Frequencies

GnomAD3 genomes

AF:

0.358

AC:

54050

AN:

150854

Hom.:

10655

Cov.:

show subpopulations

Gnomad AFR

AF:

0.215

Gnomad AMI

AF:

0.401

Gnomad AMR

AF:

0.513

Gnomad ASJ

AF:

0.364

Gnomad EAS

AF:

0.557

Gnomad SAS

AF:

0.587

Gnomad FIN

AF:

0.281

Gnomad MID

AF:

0.350

Gnomad NFE

AF:

0.390

Gnomad OTH

AF:

0.371

GnomAD2 exomes

AF:

0.368

AC:

57115

AN:

155092

AF XY:

0.370

show subpopulations

Gnomad AFR exome

AF:

0.216

Gnomad AMR exome

AF:

0.499

Gnomad ASJ exome

AF:

0.333

Gnomad EAS exome

AF:

0.467

Gnomad FIN exome

AF:

0.252

Gnomad NFE exome

AF:

0.346

Gnomad OTH exome

AF:

0.354

GnomAD4 exome

AF:

0.364

AC:

469211

AN:

1288444

Hom.:

53961

Cov.:

AF XY:

0.367

AC XY:

233205

AN XY:

634988

show subpopulations

Gnomad4 AFR exome

AF:

0.219

AC:

5629

AN:

25704

Gnomad4 AMR exome

AF:

0.497

AC:

13815

AN:

27776

Gnomad4 ASJ exome

AF:

0.335

AC:

7097

AN:

21216

Gnomad4 EAS exome

AF:

0.470

AC:

16382

AN:

34888

Gnomad4 SAS exome

AF:

0.501

AC:

32755

AN:

65370

Gnomad4 FIN exome

AF:

0.260

AC:

12649

AN:

48560

Gnomad4 NFE exome

AF:

0.357

AC:

359950

AN:

1007406

Gnomad4 Remaining exome

AF:

0.365

AC:

19219

AN:

52678

Heterozygous variant carriers

15611

31222

46832

62443

78054

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

12926

25852

38778

51704

64630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.358

AC:

54095

AN:

150956

Hom.:

10664

Cov.:

AF XY:

0.365

AC XY:

26884

AN XY:

73690

show subpopulations

Gnomad4 AFR

AF:

0.215

AC:

0.214691

AN:

0.214691

Gnomad4 AMR

AF:

0.514

AC:

0.514111

AN:

0.514111

Gnomad4 ASJ

AF:

0.364

AC:

0.364319

AN:

0.364319

Gnomad4 EAS

AF:

0.557

AC:

0.557098

AN:

0.557098

Gnomad4 SAS

AF:

0.587

AC:

0.586703

AN:

0.586703

Gnomad4 FIN

AF:

0.281

AC:

0.280552

AN:

0.280552

Gnomad4 NFE

AF:

0.390

AC:

0.390059

AN:

0.390059

Gnomad4 OTH

AF:

0.373

AC:

0.373084

AN:

0.373084

Heterozygous variant carriers

1660

3320

4981

6641

8301

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

534

1068

1602

2136

2670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.308

Hom.:

365

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=100/0

polymorphism (auto)

Splicing

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.

17-13496169-AT-ATTT

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