chr17-14301535-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006041.3(HS3ST3B1):ā€‹c.17G>Cā€‹(p.Ser6Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000211 in 1,420,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

HS3ST3B1
NM_006041.3 missense

Scores

2
3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.62
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15187141).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HS3ST3B1NM_006041.3 linkuse as main transcriptc.17G>C p.Ser6Thr missense_variant 1/2 ENST00000360954.3
HS3ST3B1NR_130138.2 linkuse as main transcriptn.455G>C 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.17G>C p.Ser6Thr missense_variant 1/21 NM_006041.3 P1
HS3ST3B1ENST00000466596.5 linkuse as main transcriptc.17G>C p.Ser6Thr missense_variant, NMD_transcript_variant 1/32

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000211
AC:
3
AN:
1420412
Hom.:
0
Cov.:
31
AF XY:
0.00000425
AC XY:
3
AN XY:
705088
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00000273
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

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 GeneticsDec 19, 2023The c.17G>C (p.S6T) alteration is located in exon 1 (coding exon 1) of the HS3ST3B1 gene. This alteration results from a G to C substitution at nucleotide position 17, causing the serine (S) at amino acid position 6 to be replaced by a threonine (T). 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
0.081
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0063
T
Eigen
Benign
-0.12
Eigen_PC
Benign
0.033
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.45
T
M_CAP
Uncertain
0.18
D
MetaRNN
Benign
0.15
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L
MutationTaster
Benign
1.0
N
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
-0.49
N
REVEL
Benign
0.039
Sift
Pathogenic
0.0
D
Sift4G
Benign
0.41
T
Polyphen
0.12
B
Vest4
0.21
MutPred
0.12
Gain of sheet (P = 0.0477);
MVP
0.54
ClinPred
0.56
D
GERP RS
4.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.28
gMVP
0.52

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: rs1325257609; hg19: chr17-14204852; API