rs62056073
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_006041.3(HS3ST3B1):c.586A>G(p.Ile196Val) variant causes a missense change. The variant allele was found at a frequency of 0.0243 in 1,587,252 control chromosomes in the GnomAD database, including 566 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.017 ( 33 hom., cov: 31)
Exomes 𝑓: 0.025 ( 533 hom. )
Consequence
HS3ST3B1
NM_006041.3 missense
NM_006041.3 missense
Scores
4
14
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 5.01
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 Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.006789446).
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0171 (2599/152150) while in subpopulation SAS AF= 0.0428 (206/4818). AF 95% confidence interval is 0.038. There are 33 homozygotes in gnomad4. There are 1268 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 33 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HS3ST3B1 | NM_006041.3 | c.586A>G | p.Ile196Val | missense_variant | 2/2 | ENST00000360954.3 | |
HS3ST3B1 | XM_017025479.3 | c.25A>G | p.Ile9Val | missense_variant | 2/2 | ||
HS3ST3B1 | NR_130138.2 | n.1024A>G | non_coding_transcript_exon_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HS3ST3B1 | ENST00000360954.3 | c.586A>G | p.Ile196Val | missense_variant | 2/2 | 1 | NM_006041.3 | P1 | |
HS3ST3B1 | ENST00000466596.5 | c.586A>G | p.Ile196Val | missense_variant, NMD_transcript_variant | 2/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0171 AC: 2599AN: 152032Hom.: 33 Cov.: 31
GnomAD3 genomes
?
AF:
AC:
2599
AN:
152032
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0202 AC: 4682AN: 231756Hom.: 76 AF XY: 0.0222 AC XY: 2764AN XY: 124636
GnomAD3 exomes
AF:
AC:
4682
AN:
231756
Hom.:
AF XY:
AC XY:
2764
AN XY:
124636
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0251 AC: 36020AN: 1435102Hom.: 533 Cov.: 32 AF XY: 0.0258 AC XY: 18359AN XY: 711168
GnomAD4 exome
AF:
AC:
36020
AN:
1435102
Hom.:
Cov.:
32
AF XY:
AC XY:
18359
AN XY:
711168
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0171 AC: 2599AN: 152150Hom.: 33 Cov.: 31 AF XY: 0.0171 AC XY: 1268AN XY: 74364
GnomAD4 genome
?
AF:
AC:
2599
AN:
152150
Hom.:
Cov.:
31
AF XY:
AC XY:
1268
AN XY:
74364
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
126
ALSPAC
AF:
AC:
102
ESP6500AA
AF:
AC:
19
ESP6500EA
AF:
AC:
233
ExAC
?
AF:
AC:
2630
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
ClinPred
T
GERP RS
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