Genetic Variant HS3ST4:p.Pro115Ser (chr16-25692760-C-T) – 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.343C>T(p.Pro115Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000224 in 1,339,448 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. P115A) has been classified as Uncertain significance.

Frequency

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

Exomes 𝑓: 0.0000017 ( 0 hom. )

Consequence

HS3ST4
NM_006040.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.307

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=0.13601762).

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.343C>T	p.Pro115Ser	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.343C>T	p.Pro115Ser	missense	Exon 1 of 2	ENSP00000330606.5	Q9Y661
ENSG00000310159	ENST00000847723.1		n.-59G>A		upstream_gene	N/A
ENSG00000310159	ENST00000847724.1		n.-59G>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000661

AC:

AN:

151364

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000168

AC:

AN:

1188084

Hom.:

Cov.:

AF XY:

0.00000174

AC XY:

AN XY:

576364

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23428

American (AMR)

AF:

0.00

AC:

AN:

11010

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16754

East Asian (EAS)

AF:

0.00

AC:

AN:

26756

South Asian (SAS)

AF:

0.00

AC:

AN:

44314

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28006

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3314

European-Non Finnish (NFE)

AF:

0.00000203

AC:

AN:

986222

Other (OTH)

AF:

0.00

AC:

AN:

48280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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:

0.00000661

AC:

AN:

151364

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73916

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41342

American (AMR)

AF:

0.00

AC:

AN:

15212

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5098

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10262

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67842

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

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:

0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.00041

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.50

M_CAP

Pathogenic

0.30

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

0.31

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.13

REVEL

Benign

0.056

Sift

Uncertain

0.016

Sift4G

Benign

0.12

Polyphen

0.65

Vest4

0.15

MutPred

0.23

Gain of phosphorylation at P115 (P = 0.0108)

MVP

0.40

MPC

1.7

ClinPred

0.22

GERP RS

2.4

Varity_R

0.12

gMVP

0.32

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over