Genetic Variant HS3ST3A1:c.*27dupA (chr17-13496169-A-AT) – 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.*27dupA 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

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 (AFR) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
HS3ST3A1	NM_006042.3 link	c.*27dupA	3_prime_UTR_variant	Exon 2 of 2	ENST00000284110.2	NP_006033.1	Q9Y663
HS3ST3A1	XM_011524114.4 link	c.*27dupA	3_prime_UTR_variant	Exon 3 of 3		XP_011522416.1
HS3ST3A1	XM_047437228.1 link	c.*27dupA	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.*27dupA	3_prime_UTR_variant	Exon 2 of 2	1	NM_006042.3	ENSP00000284110.1	Q9Y663
HS3ST3A1	ENST00000578576.1 link	c.*27dupA	splice_region_variant	Exon 2 of 2	3		ENSP00000462696.1	J3KSX5
HS3ST3A1	ENST00000578576 link	c.*27dupA	3_prime_UTR_variant	Exon 2 of 2	3		ENSP00000462696.1	J3KSX5

Frequencies

GnomAD3 genomes

AF:

0.383

AC:

57762

AN:

150880

Hom.:

13059

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.320

AC:

49649

AN:

155092

AF XY:

0.318

show subpopulations

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 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.:

AF XY:

0.289

AC XY:

181266

AN XY:

626856

show subpopulations

Gnomad4 AFR exome

AF:

0.615

AC:

16217

AN:

26378

Gnomad4 AMR exome

AF:

0.278

AC:

7420

AN:

26734

Gnomad4 ASJ exome

AF:

0.342

AC:

7184

AN:

21008

Gnomad4 EAS exome

AF:

0.202

AC:

6748

AN:

33482

Gnomad4 SAS exome

AF:

0.271

AC:

17294

AN:

63722

Gnomad4 FIN exome

AF:

0.240

AC:

11531

AN:

48142

Gnomad4 NFE exome

AF:

0.286

AC:

284809

AN:

995594

Gnomad4 Remaining exome

AF:

0.311

AC:

16216

AN:

52100

Heterozygous variant carriers

12965

25931

38896

51862

64827

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

10210

20420

30630

40840

51050

<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:

0.383

AC:

57826

AN:

150984

Hom.:

13079

Cov.:

AF XY:

0.374

AC XY:

27543

AN XY:

73708

show subpopulations

Gnomad4 AFR

AF:

0.648

AC:

0.647619

AN:

0.647619

Gnomad4 AMR

AF:

0.304

AC:

0.303626

AN:

0.303626

Gnomad4 ASJ

AF:

0.338

AC:

0.33776

AN:

0.33776

Gnomad4 EAS

AF:

0.178

AC:

0.177943

AN:

0.177943

Gnomad4 SAS

AF:

0.244

AC:

0.243958

AN:

0.243958

Gnomad4 FIN

AF:

0.238

AC:

0.237825

AN:

0.237825

Gnomad4 NFE

AF:

0.290

AC:

0.28988

AN:

0.28988

Gnomad4 OTH

AF:

0.396

AC:

0.396453

AN:

0.396453

Heterozygous variant carriers

1631

3262

4893

6524

8155

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

528

1056

1584

2112

2640

<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:

0.225

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

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