Genetic Variant NM_006040.3:c.321C>A (chr16-25692738-C-A) – 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>A(p.Ser107Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000148 in 1,283,182 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. Variant has been reported in ClinVar as Uncertain significance (★). 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 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

HS3ST4
NM_006040.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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=0.19141188).

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>A	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>A	p.Ser107Arg	missense	Exon 1 of 2	ENSP00000330606.5	Q9Y661
ENSG00000310159	ENST00000847723.1		n.-37G>T		upstream_gene	N/A
ENSG00000310159	ENST00000847724.1		n.-37G>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000199

AC:

AN:

150850

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000443

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000141

AC:

AN:

1132332

Hom.:

Cov.:

AF XY:

0.0000183

AC XY:

AN XY:

546732

show subpopulations

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:

0.0000147

AC:

AN:

951582

Other (OTH)

AF:

0.0000442

AC:

AN:

45212

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000199

AC:

AN:

150850

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73644

show subpopulations

African (AFR)

AF:

0.00

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:

0.0000443

AC:

AN:

67690

Other (OTH)

AF:

0.00

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

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

0.59

LIST_S2

Benign

0.47

M_CAP

Pathogenic

0.35

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

0.31

MPC

2.2

ClinPred

0.75

GERP RS

1.4

Varity_R

0.32

gMVP

0.22

Mutation Taster

=73/27

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over