chr17-14301535-G-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006041.3(HS3ST3B1):āc.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
NM_006041.3 missense
Scores
2
3
14
Clinical Significance
Conservation
PhyloP100: 2.62
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]
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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 |
---|---|---|---|---|---|---|---|
HS3ST3B1 | NM_006041.3 | c.17G>C | p.Ser6Thr | missense_variant | 1/2 | ENST00000360954.3 | |
HS3ST3B1 | NR_130138.2 | n.455G>C | non_coding_transcript_exon_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HS3ST3B1 | ENST00000360954.3 | c.17G>C | p.Ser6Thr | missense_variant | 1/2 | 1 | NM_006041.3 | P1 | |
HS3ST3B1 | ENST00000466596.5 | c.17G>C | p.Ser6Thr | missense_variant, NMD_transcript_variant | 1/3 | 2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000211 AC: 3AN: 1420412Hom.: 0 Cov.: 31 AF XY: 0.00000425 AC XY: 3AN XY: 705088
GnomAD4 exome
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3
AN:
1420412
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Cov.:
31
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3
AN XY:
705088
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 33
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 submitter | clinical testing | Ambry Genetics | Dec 19, 2023 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
N
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Gain of sheet (P = 0.0477);
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at