Genetic Variant NM_006041.3:c.22G>T (chr17-14301540-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_006041.3(HS3ST3B1):c.22G>T(p.Gly8Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 1,576,320 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000027 ( 1 hom. )

Consequence

HS3ST3B1
NM_006041.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.474

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]

HS3ST3B1 links:

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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=0.049048066).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS3ST3B1	NM_006041.3 link	c.22G>T	p.Gly8Cys	missense_variant	Exon 1 of 2	ENST00000360954.3	NP_006032.1	Q9Y662
HS3ST3B1	NR_130138.2 link	n.460G>T		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HS3ST3B1	ENST00000360954.3 link	c.22G>T	p.Gly8Cys	missense_variant	Exon 1 of 2	1	NM_006041.3	ENSP00000354213.2		Q9Y662
HS3ST3B1	ENST00000466596.5 link	n.22G>T		non_coding_transcript_exon_variant	Exon 1 of 3	2		ENSP00000436078.1		Q9Y662

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000274

AC:

AN:

1424278

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

707376

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:

0.0000336

Gnomad4 OTH exome

AF:

0.0000337

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152042

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74256

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.00000908

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0044

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.49

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.049

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.68

REVEL

Benign

0.079

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.042

Polyphen

0.0

Vest4

0.13

MutPred

0.20

Loss of methylation at R9 (P = 0.0526);

MVP

0.17

ClinPred

0.47

GERP RS

-2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.17

gMVP

0.58

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over