dbSNP rs60532842: HS3ST3A1:p.Ala85Ser (chr17-13600877-C-A) – 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.253G>T(p.Ala85Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 1,464,872 control chromosomes in the GnomAD database, including 458 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.012 ( 67 hom., cov: 33)

Exomes 𝑓: 0.012 ( 391 hom. )

Consequence

HS3ST3A1
NM_006042.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.42

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 (MetaRNN=0.0013333857).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS3ST3A1	NM_006042.3 link	c.253G>T	p.Ala85Ser	missense_variant	Exon 1 of 2	ENST00000284110.2	NP_006033.1
HS3ST3A1	XM_017025480.3 link	c.253G>T	p.Ala85Ser	missense_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.253G>T	p.Ala85Ser	missense_variant	Exon 1 of 2	1	NM_006042.3	ENSP00000284110.1

Frequencies

GnomAD3 genomes

AF:

0.0119

AC:

1812

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00270

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00425

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.0518

Gnomad FIN

AF:

0.0192

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00729

Gnomad OTH

AF:

0.0124

GnomAD2 exomes

AF:

0.0210

AC:

1319

AN:

62734

AF XY:

0.0222

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00552

Gnomad ASJ exome

AF:

0.00273

Gnomad EAS exome

AF:

0.123

Gnomad FIN exome

AF:

0.0221

Gnomad NFE exome

AF:

0.00713

Gnomad OTH exome

AF:

0.0166

GnomAD4 exome

AF:

0.0123

AC:

16180

AN:

1312658

Hom.:

391

Cov.:

AF XY:

0.0132

AC XY:

8534

AN XY:

645752

show subpopulations

African (AFR)

AF:

0.00176

AC:

AN:

25614

American (AMR)

AF:

0.00431

AC:

AN:

20176

Ashkenazi Jewish (ASJ)

AF:

0.00356

AC:

AN:

20800

East Asian (EAS)

AF:

0.117

AC:

3460

AN:

29530

South Asian (SAS)

AF:

0.0457

AC:

3092

AN:

67696

European-Finnish (FIN)

AF:

0.0232

AC:

976

AN:

42100

Middle Eastern (MID)

AF:

0.00867

AC:

AN:

3922

European-Non Finnish (NFE)

AF:

0.00707

AC:

7412

AN:

1048732

Other (OTH)

AF:

0.0185

AC:

1000

AN:

54088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

971

1943

2914

3886

4857

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

338

676

1014

1352

1690

<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:

0.0119

AC:

1811

AN:

152214

Hom.:

Cov.:

AF XY:

0.0132

AC XY:

984

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.00269

AC:

112

AN:

41566

American (AMR)

AF:

0.00425

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3468

East Asian (EAS)

AF:

0.125

AC:

643

AN:

5134

South Asian (SAS)

AF:

0.0518

AC:

250

AN:

4824

European-Finnish (FIN)

AF:

0.0192

AC:

204

AN:

10604

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00729

AC:

496

AN:

67998

Other (OTH)

AF:

0.0132

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

168

251

335

419

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.00321

Hom.:

Bravo

AF:

0.00906

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00701

AC:

ExAC

AF:

0.0175

AC:

359

Asia WGS

AF:

0.0890

AC:

306

AN:

3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.51

MetaRNN

Benign

0.0013

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.46

PhyloP100

3.4

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

0.22

REVEL

Benign

0.076

Sift

Benign

0.56

Sift4G

Benign

0.86

Polyphen

0.42

Vest4

0.042

ClinPred

0.038

GERP RS

2.6

Varity_R

0.079

gMVP

0.34

Mutation Taster

=98/2

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