Genetic Variant HS3ST3A1:c.-219T>C (chr17-13601348-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006042.3(HS3ST3A1):c.-219T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 488,678 control chromosomes in the GnomAD database, including 15,038 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 0.25 ( 5146 hom., cov: 33)

Exomes 𝑓: 0.23 ( 9892 hom. )

Consequence

HS3ST3A1
NM_006042.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.113

Publications

6 publications found

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS3ST3A1	NM_006042.3 link	c.-219T>C		5_prime_UTR_variant	Exon 1 of 2	ENST00000284110.2	NP_006033.1	Q9Y663
HS3ST3A1	XM_017025480.3 link	c.-219T>C		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.-219T>C		5_prime_UTR_variant	Exon 1 of 2	1	NM_006042.3	ENSP00000284110.1		Q9Y663

Frequencies

GnomAD3 genomes

AF:

0.255

AC:

38690

AN:

151938

Hom.:

5134

Cov.:

show subpopulations

Gnomad AFR

AF:

0.316

Gnomad AMI

AF:

0.282

Gnomad AMR

AF:

0.191

Gnomad ASJ

AF:

0.223

Gnomad EAS

AF:

0.0843

Gnomad SAS

AF:

0.202

Gnomad FIN

AF:

0.203

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.258

Gnomad OTH

AF:

0.244

GnomAD4 exome

AF:

0.235

AC:

78941

AN:

336622

Hom.:

9892

Cov.:

AF XY:

0.233

AC XY:

41035

AN XY:

175868

show subpopulations

African (AFR)

AF:

0.310

AC:

2250

AN:

7254

American (AMR)

AF:

0.168

AC:

1398

AN:

8304

Ashkenazi Jewish (ASJ)

AF:

0.226

AC:

2449

AN:

10828

East Asian (EAS)

AF:

0.110

AC:

2527

AN:

23006

South Asian (SAS)

AF:

0.211

AC:

5153

AN:

24450

European-Finnish (FIN)

AF:

0.202

AC:

5358

AN:

26580

Middle Eastern (MID)

AF:

0.232

AC:

377

AN:

1626

European-Non Finnish (NFE)

AF:

0.255

AC:

54417

AN:

213760

Other (OTH)

AF:

0.241

AC:

5012

AN:

20814

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

2855

5709

8564

11418

14273

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

204

408

612

816

1020

<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:

0.255

AC:

38738

AN:

152056

Hom.:

5146

Cov.:

AF XY:

0.247

AC XY:

18350

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.316

AC:

13106

AN:

41488

American (AMR)

AF:

0.191

AC:

2917

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.223

AC:

774

AN:

3466

East Asian (EAS)

AF:

0.0845

AC:

432

AN:

5112

South Asian (SAS)

AF:

0.202

AC:

974

AN:

4818

European-Finnish (FIN)

AF:

0.203

AC:

2156

AN:

10606

Middle Eastern (MID)

AF:

0.252

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.258

AC:

17522

AN:

67950

Other (OTH)

AF:

0.249

AC:

527

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1557

3114

4671

6228

7785

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

402

804

1206

1608

2010

<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:

0.261

Hom.:

680

Bravo

AF:

0.256

Asia WGS

AF:

0.171

AC:

596

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

9.5

(source)

DANN

Benign

0.70

PhyloP100

0.11

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over