Variant 13-96090995-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000376705.4(HS6ST3):c.133G>A(p.Glu45Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00106 in 1,320,656 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00069 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0011 ( 1 hom. )

Consequence

HS6ST3
ENST00000376705.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.16

Variant links:

Genes affected

HS6ST3 (HGNC:19134): (heparan sulfate 6-O-sulfotransferase 3) Heparan sulfate (HS) sulfotransferases, such as HS6ST3, modify HS to generate structures required for interactions between HS and a variety of proteins. These interactions are implicated in proliferation and differentiation, adhesion, migration, inflammation, blood coagulation, and other diverse processes (Habuchi et al., 2000 [PubMed 10644753]).[supplied by OMIM, Mar 2008]

HS6ST3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021417677).

BS2

High AC in GnomAd4 at 103 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HS6ST3	NM_153456.4 linkuse as main transcript	c.133G>A	p.Glu45Lys	missense_variant	1/2	ENST00000376705.4	NP_703157.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HS6ST3	ENST00000376705.4 linkuse as main transcript	c.133G>A	p.Glu45Lys	missense_variant	1/2	1	NM_153456.4	ENSP00000365895	P1

Frequencies

GnomAD3 genomes

AF:

0.000687

AC:

103

AN:

149906

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000663

Gnomad ASJ

AF:

0.00404

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000203

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00116

Gnomad OTH

AF:

0.000487

GnomAD3 exomes

AF:

0.000805

AC:

AN:

112992

Hom.:

AF XY:

0.000689

AC XY:

AN XY:

63862

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.0000940

Gnomad ASJ exome

AF:

0.00405

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000716

Gnomad NFE exome

AF:

0.00130

Gnomad OTH exome

AF:

0.000951

GnomAD4 exome

AF:

0.00111

AC:

1299

AN:

1170750

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

608

AN XY:

568744

show subpopulations

Gnomad4 AFR exome

AF:

0.000123

Gnomad4 AMR exome

AF:

0.0000544

Gnomad4 ASJ exome

AF:

0.00459

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000292

Gnomad4 FIN exome

AF:

0.0000791

Gnomad4 NFE exome

AF:

0.00124

Gnomad4 OTH exome

AF:

0.000700

GnomAD4 genome

AF:

0.000687

AC:

103

AN:

149906

Hom.:

Cov.:

AF XY:

0.000560

AC XY:

AN XY:

73154

show subpopulations

Gnomad4 AFR

AF:

0.000170

Gnomad4 AMR

AF:

0.0000663

Gnomad4 ASJ

AF:

0.00404

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000203

Gnomad4 NFE

AF:

0.00116

Gnomad4 OTH

AF:

0.000487

Alfa

AF:

0.00101

Hom.:

Bravo

AF:

0.000567

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.000683

AC:

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

Aug 09, 2021

The c.133G>A (p.E45K) alteration is located in exon 1 (coding exon 1) of the HS6ST3 gene. This alteration results from a G to A substitution at nucleotide position 133, causing the glutamic acid (E) at amino acid position 45 to be replaced by a lysine (K). 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

0.13

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0092

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.64

M_CAP

Pathogenic

0.94

MetaRNN

Benign

0.021

MetaSVM

Benign

-0.31

MutationAssessor

Benign

0.81

MutationTaster

Benign

0.54

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.51

REVEL

Benign

0.21

Sift

Uncertain

0.0080

Sift4G

Benign

0.070

Polyphen

0.018

Vest4

0.19

MVP

0.13

MPC

0.60

ClinPred

0.029

GERP RS

3.5

Varity_R

0.31

gMVP

0.31

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