Genetic Variant HS3ST4:p.Ser107Arg (chr16-25692738-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006040.3(HS3ST4):c.321C>G(p.Ser107Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000663 in 150,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S107N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HS3ST4
NM_006040.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.575

Publications

0 publications found

Variant links:

Genes affected

HS3ST4 (HGNC:5200): (heparan sulfate-glucosamine 3-sulfotransferase 4) This gene encodes the enzyme heparan sulfate D-glucosaminyl 3-O-sulfotransferase 4. This enzyme generates 3-O-sulfated glucosaminyl residues in heparan sulfate. Cell surface heparan sulfate is used as a receptor by herpes simplex virus type 1 (HSV-1), and expression of this gene is thought to play a role in HSV-1 pathogenesis. [provided by RefSeq, Jul 2008]

HS3ST4 links:

ENSG00000310159 (HGNC:):

ENSG00000310159 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18837228).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006040.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST4	NM_006040.3	MANE Select	c.321C>G	p.Ser107Arg	missense	Exon 1 of 2	NP_006031.2	Q9Y661

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HS3ST4	ENST00000331351.6	TSL:1 MANE Select	c.321C>G	p.Ser107Arg	missense	Exon 1 of 2	ENSP00000330606.5	Q9Y661
ENSG00000310159	ENST00000847723.1		n.-37G>C		upstream_gene	N/A
ENSG00000310159	ENST00000847724.1		n.-37G>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000663

AC:

AN:

150850

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1132332

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

546732

African (AFR)

AF:

0.00

AC:

AN:

22870

American (AMR)

AF:

0.00

AC:

AN:

13036

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15776

East Asian (EAS)

AF:

0.00

AC:

AN:

25338

South Asian (SAS)

AF:

0.00

AC:

AN:

31446

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24046

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3026

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

951582

Other (OTH)

AF:

0.00

AC:

AN:

45212

GnomAD4 genome

AF:

0.00000663

AC:

AN:

150850

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73644

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41288

American (AMR)

AF:

0.00

AC:

AN:

15148

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5074

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10068

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67690

Other (OTH)

AF:

0.00

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0055

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.47

M_CAP

Pathogenic

0.34

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.55

PhyloP100

0.57

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-1.0

REVEL

Benign

0.094

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.032

Polyphen

0.97

Vest4

0.11

MutPred

0.17

Loss of phosphorylation at S107 (P = 0.0084)

MVP

0.28

MPC

2.2

ClinPred

0.67

GERP RS

1.4

Varity_R

0.32

gMVP

0.22

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over