Genetic Variant NM_006042.3:c.-243A>T (chr17-13601372-T-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_006042.3(HS3ST3A1):c.-243A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0177 in 471,604 control chromosomes in the GnomAD database, including 303 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 0.012 ( 74 hom., cov: 33)

Exomes 𝑓: 0.020 ( 229 hom. )

Consequence

HS3ST3A1
NM_006042.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.51

Publications

2 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS3ST3A1	NM_006042.3 link	c.-243A>T		5_prime_UTR_variant	Exon 1 of 2	ENST00000284110.2	NP_006033.1	Q9Y663
HS3ST3A1	XM_017025480.3 link	c.-243A>T		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.-243A>T		5_prime_UTR_variant	Exon 1 of 2	1	NM_006042.3	ENSP00000284110.1		Q9Y663

Frequencies

GnomAD3 genomes

AF:

0.0123

AC:

1870

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00425

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.126

Gnomad SAS

AF:

0.0639

Gnomad FIN

AF:

0.0193

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00722

Gnomad OTH

AF:

0.0134

GnomAD4 exome

AF:

0.0203

AC:

6489

AN:

319336

Hom.:

229

Cov.:

AF XY:

0.0213

AC XY:

3533

AN XY:

166084

show subpopulations

African (AFR)

AF:

0.00302

AC:

AN:

6964

American (AMR)

AF:

0.00357

AC:

AN:

7854

Ashkenazi Jewish (ASJ)

AF:

0.00431

AC:

AN:

10434

East Asian (EAS)

AF:

0.116

AC:

2561

AN:

22006

South Asian (SAS)

AF:

0.0549

AC:

1231

AN:

22430

European-Finnish (FIN)

AF:

0.0242

AC:

612

AN:

25284

Middle Eastern (MID)

AF:

0.00960

AC:

AN:

1562

European-Non Finnish (NFE)

AF:

0.00778

AC:

1580

AN:

202980

Other (OTH)

AF:

0.0200

AC:

396

AN:

19822

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

285

570

856

1141

1426

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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:

0.0123

AC:

1872

AN:

152268

Hom.:

Cov.:

AF XY:

0.0138

AC XY:

1031

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.00265

AC:

110

AN:

41584

American (AMR)

AF:

0.00425

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3468

East Asian (EAS)

AF:

0.126

AC:

648

AN:

5132

South Asian (SAS)

AF:

0.0642

AC:

310

AN:

4832

European-Finnish (FIN)

AF:

0.0193

AC:

205

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00722

AC:

491

AN:

68004

Other (OTH)

AF:

0.0142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

187

280

374

467

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.00868

Hom.:

Bravo

AF:

0.00909

Asia WGS

AF:

0.0980

AC:

338

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

2.5

Mutation Taster

=299/1

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