rs921525067

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_153456.4(HS6ST3):​c.200G>A​(p.Arg67Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000866 in 1,269,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000054 ( 0 hom. )

Consequence

HS6ST3
NM_153456.4 missense

Scores

2
1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.165

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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.12983966).
BS2
High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HS6ST3NM_153456.4 linkc.200G>A p.Arg67Gln 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
HS6ST3ENST00000376705.4 linkc.200G>A p.Arg67Gln missense_variant Exon 1 of 2 1 NM_153456.4 ENSP00000365895.2 Q8IZP7

Frequencies

GnomAD3 genomes
AF:
0.0000334
AC:
5
AN:
149830
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000122
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000536
AC:
6
AN:
1119876
Hom.:
0
Cov.:
32
AF XY:
0.00000748
AC XY:
4
AN XY:
535106
show subpopulations
African (AFR)
AF:
0.000218
AC:
5
AN:
22976
American (AMR)
AF:
0.00
AC:
0
AN:
8480
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
14668
East Asian (EAS)
AF:
0.00
AC:
0
AN:
26776
South Asian (SAS)
AF:
0.00
AC:
0
AN:
27518
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
27224
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3724
European-Non Finnish (NFE)
AF:
0.00000106
AC:
1
AN:
943580
Other (OTH)
AF:
0.00
AC:
0
AN:
44930
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.483
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000334
AC:
5
AN:
149830
Hom.:
0
Cov.:
31
AF XY:
0.0000410
AC XY:
3
AN XY:
73112
show subpopulations
African (AFR)
AF:
0.000122
AC:
5
AN:
41018
American (AMR)
AF:
0.00
AC:
0
AN:
15082
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3462
East Asian (EAS)
AF:
0.00
AC:
0
AN:
4934
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4788
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
9968
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
306
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67292
Other (OTH)
AF:
0.00
AC:
0
AN:
2072
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.555
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000453

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 07, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.200G>A (p.R67Q) 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 200, causing the arginine (R) at amino acid position 67 to be replaced by a glutamine (Q). 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
0.10
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0056
T
Eigen
Benign
-0.55
Eigen_PC
Benign
-0.41
FATHMM_MKL
Benign
0.48
N
LIST_S2
Benign
0.66
T
M_CAP
Pathogenic
0.90
D
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
0.69
N
PhyloP100
0.17
PrimateAI
Pathogenic
0.93
D
PROVEAN
Benign
0.010
N
REVEL
Benign
0.089
Sift
Benign
0.35
T
Sift4G
Benign
0.59
T
Polyphen
0.023
B
Vest4
0.21
MutPred
0.24
Gain of catalytic residue at P72 (P = 5e-04);
MVP
0.31
MPC
0.61
ClinPred
0.33
T
GERP RS
2.1
Varity_R
0.040
gMVP
0.13
Mutation Taster
=88/12
polymorphism

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

Other links and lift over

dbSNP: rs921525067; hg19: chr13-96743316; API