Genetic Variant HS6ST3:p.Ile21Leu (chr13-96090923-A-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_153456.4(HS6ST3):c.61A>C(p.Ile21Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000119 in 1,508,278 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

HS6ST3
NM_153456.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.80

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS6ST3	NM_153456.4 link	c.61A>C	p.Ile21Leu	missense_variant	Exon 1 of 2	ENST00000376705.4	NP_703157.2	Q8IZP7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HS6ST3	ENST00000376705.4 link	c.61A>C	p.Ile21Leu	missense_variant	Exon 1 of 2	1	NM_153456.4	ENSP00000365895.2		Q8IZP7

Frequencies

GnomAD3 genomes

AF:

0.00000666

AC:

AN:

150184

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000261

AC:

AN:

191542

AF XY:

0.0000282

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000568

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000125

AC:

AN:

1358094

Hom.:

Cov.:

AF XY:

0.0000104

AC XY:

AN XY:

676324

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27800

American (AMR)

AF:

0.00

AC:

AN:

34082

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22604

East Asian (EAS)

AF:

0.00

AC:

AN:

30306

South Asian (SAS)

AF:

0.0000129

AC:

AN:

77226

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50718

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5356

European-Non Finnish (NFE)

AF:

0.0000142

AC:

AN:

1055798

Other (OTH)

AF:

0.0000184

AC:

AN:

54204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000666

AC:

AN:

150184

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73308

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41222

American (AMR)

AF:

0.00

AC:

AN:

15112

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5066

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9812

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67398

Other (OTH)

AF:

0.00

AC:

AN:

2064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000912

Hom.:

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000413

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 17, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.61A>C (p.I21L) alteration is located in exon 1 (coding exon 1) of the HS6ST3 gene. This alteration results from a A to C substitution at nucleotide position 61, causing the isoleucine (I) at amino acid position 21 to be replaced by a leucine (L). 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

0.17

BayesDel_addAF

Benign

-0.072

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.070

Eigen

Benign

-0.036

Eigen_PC

Benign

0.043

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.48

M_CAP

Pathogenic

0.84

MetaRNN

Uncertain

0.53

MetaSVM

Benign

-0.41

MutationAssessor

Benign

0.81

PhyloP100

4.8

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.1

REVEL

Uncertain

0.36

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.011

Polyphen

0.79

Vest4

0.53

MVP

0.25

MPC

0.55

ClinPred

0.35

GERP RS

3.4

Varity_R

0.59

gMVP

0.45

Mutation Taster

=78/22

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

13-96090923-A-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over