Genetic Variant HS6ST3:p.Glu80Lys (chr13-96091100-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_153456.4(HS6ST3):c.238G>A(p.Glu80Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000671 in 149,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E80A) has been classified as Uncertain significance.

Frequency

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

Exomes 𝑓: 0.000020 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HS6ST3
NM_153456.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.75

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26873916).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS6ST3	NM_153456.4 link	c.238G>A	p.Glu80Lys	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.238G>A	p.Glu80Lys	missense_variant	Exon 1 of 2	1	NM_153456.4	ENSP00000365895.2		Q8IZP7

Frequencies

GnomAD3 genomes

AF:

0.00000671

AC:

AN:

148986

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:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

16642

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000202

AC:

AN:

1187526

Hom.:

Cov.:

AF XY:

0.0000244

AC XY:

AN XY:

574380

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23294

American (AMR)

AF:

0.00

AC:

AN:

11238

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15824

East Asian (EAS)

AF:

0.00

AC:

AN:

26272

South Asian (SAS)

AF:

0.0000208

AC:

AN:

47984

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29784

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3482

European-Non Finnish (NFE)

AF:

0.0000224

AC:

AN:

982056

Other (OTH)

AF:

0.0000210

AC:

AN:

47592

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.567

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000671

AC:

AN:

149102

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72836

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40928

American (AMR)

AF:

0.00

AC:

AN:

14976

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3452

East Asian (EAS)

AF:

0.00

AC:

AN:

4818

South Asian (SAS)

AF:

0.00

AC:

AN:

4624

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10010

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

67036

Other (OTH)

AF:

0.00

AC:

AN:

2068

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

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.036

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0072

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.67

M_CAP

Pathogenic

0.92

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.63

MutationAssessor

Benign

0.81

PhyloP100

3.7

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-0.12

REVEL

Benign

0.20

Sift

Benign

0.048

Sift4G

Benign

0.72

Polyphen

0.15

Vest4

0.31

MutPred

0.34

Gain of catalytic residue at P78 (P = 8e-04);

MVP

0.29

MPC

0.60

ClinPred

0.50

GERP RS

3.1

Varity_R

0.12

gMVP

0.46

Mutation Taster

=91/9

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

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chr13-96091100-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over