Genetic Variant HS3ST3A1:c.-438A>C (chr17-13601567-T-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.-438A>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 0.251 in 160,150 control chromosomes in the GnomAD database, including 5,244 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 ( 5010 hom., cov: 33)

Exomes 𝑓: 0.24 ( 234 hom. )

Consequence

HS3ST3A1
NM_006042.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.43

Publications

5 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=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006042.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST3A1	NM_006042.3	MANE Select	c.-438A>C		5_prime_UTR	Exon 1 of 2	NP_006033.1	Q9Y663

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST3A1	ENST00000284110.2	TSL:1 MANE Select	c.-438A>C		5_prime_UTR	Exon 1 of 2	ENSP00000284110.1	Q9Y663

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

38255

AN:

151888

Hom.:

5001

Cov.:

show subpopulations

Gnomad AFR

AF:

0.307

Gnomad AMI

AF:

0.280

Gnomad AMR

AF:

0.190

Gnomad ASJ

AF:

0.222

Gnomad EAS

AF:

0.0835

Gnomad SAS

AF:

0.201

Gnomad FIN

AF:

0.203

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.258

Gnomad OTH

AF:

0.240

GnomAD4 exome

AF:

0.236

AC:

1921

AN:

8144

Hom.:

234

Cov.:

AF XY:

0.237

AC XY:

962

AN XY:

4064

show subpopulations

African (AFR)

AF:

0.301

AC:

AN:

296

American (AMR)

AF:

0.152

AC:

AN:

164

Ashkenazi Jewish (ASJ)

AF:

0.203

AC:

AN:

310

East Asian (EAS)

AF:

0.0870

AC:

AN:

322

South Asian (SAS)

AF:

0.207

AC:

AN:

188

European-Finnish (FIN)

AF:

0.222

AC:

AN:

288

Middle Eastern (MID)

AF:

0.167

AC:

AN:

European-Non Finnish (NFE)

AF:

0.247

AC:

1483

AN:

6014

Other (OTH)

AF:

0.237

AC:

122

AN:

514

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

142

212

283

354

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.252

AC:

38295

AN:

152006

Hom.:

5010

Cov.:

AF XY:

0.244

AC XY:

18136

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.307

AC:

12725

AN:

41454

American (AMR)

AF:

0.190

AC:

2898

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.222

AC:

772

AN:

3472

East Asian (EAS)

AF:

0.0837

AC:

429

AN:

5124

South Asian (SAS)

AF:

0.202

AC:

974

AN:

4820

European-Finnish (FIN)

AF:

0.203

AC:

2147

AN:

10600

Middle Eastern (MID)

AF:

0.252

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.258

AC:

17503

AN:

67936

Other (OTH)

AF:

0.246

AC:

519

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1496

2993

4489

5986

7482

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

400

800

1200

1600

2000

<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:

0.140

Hom.:

290

Bravo

AF:

0.254

Asia WGS

AF:

0.167

AC:

583

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.18

(source)

DANN

Benign

0.35

PhyloP100

-2.4

PromoterAI

0.050

Neutral

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over