Variant 17-13496289-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006042.3(HS3ST3A1):c.1129C>A(p.Arg377Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,548,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000086 ( 0 hom. )

Consequence

HS3ST3A1
NM_006042.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.73

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.060209006).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HS3ST3A1	NM_006042.3 linkuse as main transcript	c.1129C>A	p.Arg377Ser	missense_variant	2/2	ENST00000284110.2	NP_006033.1	Q9Y663
HS3ST3A1	XM_011524114.4 linkuse as main transcript	c.532C>A	p.Arg178Ser	missense_variant	3/3		XP_011522416.1
HS3ST3A1	XM_047437228.1 linkuse as main transcript	c.532C>A	p.Arg178Ser	missense_variant	2/2		XP_047293184.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HS3ST3A1	ENST00000284110.2 linkuse as main transcript	c.1129C>A	p.Arg377Ser	missense_variant	2/2	1	NM_006042.3	ENSP00000284110.1		Q9Y663
HS3ST3A1	ENST00000578576.1 linkuse as main transcript	c.523C>A	p.Arg175Ser	missense_variant	2/2	3		ENSP00000462696.1		J3KSX5

Frequencies

GnomAD3 genomes

AF:

0.0000265

AC:

AN:

151186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000582

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000859

AC:

AN:

1396946

Hom.:

Cov.:

AF XY:

0.0000101

AC XY:

AN XY:

692396

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000396

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000831

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000265

AC:

AN:

151186

Hom.:

Cov.:

AF XY:

0.0000407

AC XY:

AN XY:

73740

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000582

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 07, 2023

The c.1129C>A (p.R377S) alteration is located in exon 2 (coding exon 2) of the HS3ST3A1 gene. This alteration results from a C to A substitution at nucleotide position 1129, causing the arginine (R) at amino acid position 377 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.088

T;.

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.76

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.060

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

-0.30

N;.

MutationTaster

Benign

0.99

N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.35

N;.

REVEL

Benign

0.17

Sift

Benign

0.084

T;.

Sift4G

Benign

0.20

T;T

Polyphen

0.0

B;.

Vest4

0.15

MutPred

0.44

Loss of MoRF binding (P = 0.0095);.;

MVP

0.061

ClinPred

0.47

GERP RS

-0.56

Varity_R

0.20

gMVP

0.28

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over