Variant 17-13496280-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006042.3(HS3ST3A1):c.1138G>A(p.Val380Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HS3ST3A1
NM_006042.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.40

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27511716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HS3ST3A1	NM_006042.3 linkuse as main transcript	c.1138G>A	p.Val380Met	missense_variant	2/2	ENST00000284110.2	NP_006033.1	Q9Y663
HS3ST3A1	XM_011524114.4 linkuse as main transcript	c.541G>A	p.Val181Met	missense_variant	3/3		XP_011522416.1
HS3ST3A1	XM_047437228.1 linkuse as main transcript	c.541G>A	p.Val181Met	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.1138G>A	p.Val380Met	missense_variant	2/2	1	NM_006042.3	ENSP00000284110.1		Q9Y663
HS3ST3A1	ENST00000578576.1 linkuse as main transcript	c.532G>A	p.Val178Met	missense_variant	2/2	3		ENSP00000462696.1		J3KSX5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000529

AC:

AN:

189166

Hom.:

AF XY:

0.00000984

AC XY:

AN XY:

101592

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000109

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000144

AC:

AN:

1389562

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

687796

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000185

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 11, 2023

The c.1138G>A (p.V380M) alteration is located in exon 2 (coding exon 2) of the HS3ST3A1 gene. This alteration results from a G to A substitution at nucleotide position 1138, causing the valine (V) at amino acid position 380 to be replaced by a methionine (M). 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

0.26

BayesDel_addAF

Benign

-0.0032

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.27

T;.

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.46

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.054

MetaRNN

Benign

0.28

T;T

MetaSVM

Benign

-0.51

MutationAssessor

Benign

0.71

N;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-2.0

N;.

REVEL

Uncertain

0.32

Sift

Benign

0.069

T;.

Sift4G

Benign

0.14

T;T

Polyphen

0.012

B;.

Vest4

0.45

MutPred

0.59

Gain of disorder (P = 0.0745);.;

MVP

0.12

ClinPred

0.17

GERP RS

-2.8

Varity_R

0.37

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