Genetic Variant NM_006042.3:c.39G>T (chr17-13601091-C-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_006042.3(HS3ST3A1):c.39G>T(p.Ser13Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 1,591,590 control chromosomes in the GnomAD database, including 556 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 0.034 ( 241 hom., cov: 33)

Exomes 𝑓: 0.010 ( 315 hom. )

Consequence

HS3ST3A1
NM_006042.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.43

Publications

1 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP7

Synonymous conserved (PhyloP=-1.43 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.098 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS3ST3A1	NM_006042.3 link	c.39G>T	p.Ser13Ser	synonymous_variant	Exon 1 of 2	ENST00000284110.2	NP_006033.1	Q9Y663
HS3ST3A1	XM_017025480.3 link	c.39G>T	p.Ser13Ser	synonymous_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.39G>T	p.Ser13Ser	synonymous_variant	Exon 1 of 2	1	NM_006042.3	ENSP00000284110.1		Q9Y663

Frequencies

GnomAD3 genomes

AF:

0.0337

AC:

5122

AN:

152138

Hom.:

238

Cov.:

show subpopulations

Gnomad AFR

AF:

0.100

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0175

Gnomad ASJ

AF:

0.0256

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.0294

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.00566

Gnomad OTH

AF:

0.0248

GnomAD2 exomes

AF:

0.0160

AC:

3341

AN:

208742

AF XY:

0.0161

show subpopulations

Gnomad AFR exome

AF:

0.104

Gnomad AMR exome

AF:

0.00857

Gnomad ASJ exome

AF:

0.0265

Gnomad EAS exome

AF:

0.0000662

Gnomad FIN exome

AF:

0.00157

Gnomad NFE exome

AF:

0.00642

Gnomad OTH exome

AF:

0.0125

GnomAD4 exome

AF:

0.0102

AC:

14744

AN:

1439344

Hom.:

315

Cov.:

AF XY:

0.0107

AC XY:

7614

AN XY:

714416

show subpopulations

African (AFR)

AF:

0.104

AC:

3339

AN:

32150

American (AMR)

AF:

0.00896

AC:

381

AN:

42510

Ashkenazi Jewish (ASJ)

AF:

0.0239

AC:

607

AN:

25418

East Asian (EAS)

AF:

0.0000530

AC:

AN:

37736

South Asian (SAS)

AF:

0.0340

AC:

2816

AN:

82818

European-Finnish (FIN)

AF:

0.00131

AC:

AN:

51094

Middle Eastern (MID)

AF:

0.0230

AC:

131

AN:

5696

European-Non Finnish (NFE)

AF:

0.00594

AC:

6553

AN:

1102542

Other (OTH)

AF:

0.0143

AC:

848

AN:

59380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

787

1574

2362

3149

3936

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0337

AC:

5136

AN:

152246

Hom.:

241

Cov.:

AF XY:

0.0336

AC XY:

2500

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.101

AC:

4177

AN:

41560

American (AMR)

AF:

0.0175

AC:

268

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0256

AC:

AN:

3470

East Asian (EAS)

AF:

0.000194

AC:

AN:

5142

South Asian (SAS)

AF:

0.0294

AC:

142

AN:

4834

European-Finnish (FIN)

AF:

0.00132

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0171

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00568

AC:

386

AN:

67996

Other (OTH)

AF:

0.0246

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

243

486

728

971

1214

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0141

Hom.:

Bravo

AF:

0.0366

Asia WGS

AF:

0.0160

AC:

AN:

3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.92

(source)

DANN

Benign

0.71

PhyloP100

-1.4

Mutation Taster

=100/0

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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NM_006042.3:c.39G>T

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