17-14301846-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006041.3(HS3ST3B1):​c.328A>T​(p.Ser110Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000597 in 1,591,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

HS3ST3B1
NM_006041.3 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.29
Variant links:
Genes affected
HS3ST3B1 (HGNC:5198): (heparan sulfate-glucosamine 3-sulfotransferase 3B1) The protein encoded by this gene is a type II integral membrane protein that belongs to the 3-O-sulfotransferases family. These proteins catalyze the addition of sulfate groups at the 3-OH position of glucosamine in heparan sulfate. The substrate specificity of individual members of the family is based on prior modification of the heparan sulfate chain, thus allowing different members of the family to generate binding sites for different proteins on the same heparan sulfate chain. Following treatment with a histone deacetylase inhibitor, expression of this gene is activated in a pancreatic cell line. The increased expression results in promotion of the epithelial-mesenchymal transition. In addition, the modification catalyzed by this protein allows herpes simplex virus membrane fusion and penetration. A very closely related homolog with an almost identical sulfotransferase domain maps less than 1 Mb away. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.020545125).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HS3ST3B1NM_006041.3 linkuse as main transcriptc.328A>T p.Ser110Cys missense_variant 1/2 ENST00000360954.3
HS3ST3B1NR_130138.2 linkuse as main transcriptn.766A>T non_coding_transcript_exon_variant 1/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HS3ST3B1ENST00000360954.3 linkuse as main transcriptc.328A>T p.Ser110Cys missense_variant 1/21 NM_006041.3 P1
HS3ST3B1ENST00000466596.5 linkuse as main transcriptc.328A>T p.Ser110Cys missense_variant, NMD_transcript_variant 1/32

Frequencies

GnomAD3 genomes
AF:
0.000388
AC:
59
AN:
152154
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00142
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
GnomAD3 exomes
AF:
0.0000870
AC:
18
AN:
206822
Hom.:
0
AF XY:
0.0000888
AC XY:
10
AN XY:
112660
show subpopulations
Gnomad AFR exome
AF:
0.00139
Gnomad AMR exome
AF:
0.0000664
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000257
AC:
37
AN:
1438980
Hom.:
0
Cov.:
31
AF XY:
0.0000280
AC XY:
20
AN XY:
713396
show subpopulations
Gnomad4 AFR exome
AF:
0.000932
Gnomad4 AMR exome
AF:
0.0000489
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:
0.00
Gnomad4 OTH exome
AF:
0.0000671
GnomAD4 genome
AF:
0.000381
AC:
58
AN:
152274
Hom.:
0
Cov.:
33
AF XY:
0.000376
AC XY:
28
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.00140
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000442
ESP6500AA
AF:
0.00161
AC:
7
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000913
AC:
11

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 submitterclinical testingAmbry GeneticsAug 12, 2021The c.328A>T (p.S110C) alteration is located in exon 1 (coding exon 1) of the HS3ST3B1 gene. This alteration results from a A to T substitution at nucleotide position 328, causing the serine (S) at amino acid position 110 to be replaced by a cysteine (C). 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
-0.47
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.020
T
Eigen
Benign
0.11
Eigen_PC
Benign
0.082
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.51
T
M_CAP
Uncertain
0.26
D
MetaRNN
Benign
0.021
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
N
MutationTaster
Benign
1.0
N
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-1.5
N
REVEL
Benign
0.070
Sift
Benign
0.052
T
Sift4G
Uncertain
0.055
T
Polyphen
0.98
D
Vest4
0.17
MVP
0.67
ClinPred
0.057
T
GERP RS
4.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.064
gMVP
0.63

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.

Other links and lift over

dbSNP: rs200811372; hg19: chr17-14205163; API