Genetic Variant NM_006042.3:c.253G>T (chr17-13600877-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -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. 12/19 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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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	Q9Y663
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		Q9Y663

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

GnomAD3 exomes

AF:

0.0210

AC:

1319

AN:

62734

Hom.:

AF XY:

0.0222

AC XY:

800

AN XY:

36014

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 SAS exome

AF:

0.0483

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

Gnomad4 AFR exome

AF:

0.00176

Gnomad4 AMR exome

AF:

0.00431

Gnomad4 ASJ exome

AF:

0.00356

Gnomad4 EAS exome

AF:

0.117

Gnomad4 SAS exome

AF:

0.0457

Gnomad4 FIN exome

AF:

0.0232

Gnomad4 NFE exome

AF:

0.00707

Gnomad4 OTH exome

AF:

0.0185

GnomAD4 genome

AF:

0.0119

AC:

1811

AN:

152214

Hom.:

Cov.:

AF XY:

0.0132

AC XY:

984

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.00269

Gnomad4 AMR

AF:

0.00425

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.125

Gnomad4 SAS

AF:

0.0518

Gnomad4 FIN

AF:

0.0192

Gnomad4 NFE

AF:

0.00729

Gnomad4 OTH

AF:

0.0132

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

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

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over