Genetic Variant NM_006040.3:c.5C>T (chr16-25692422-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.5C>T(p.Ala2Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000492 in 1,055,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000083 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

HS3ST4
NM_006040.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.915

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=0.16285983).

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.5C>T	p.Ala2Val	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.5C>T	p.Ala2Val	missense	Exon 1 of 2	ENSP00000330606.5	Q9Y661
ENSG00000310159	ENST00000847723.1		n.143+137G>A		intron	N/A
ENSG00000310159	ENST00000847724.1		n.143+137G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000826

AC:

AN:

145352

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000745

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:

0.000137

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000224

AC:

AN:

4472

AF XY:

0.000374

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000321

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000439

AC:

AN:

910640

Hom.:

Cov.:

AF XY:

0.0000459

AC XY:

AN XY:

435456

show subpopulations

African (AFR)

AF:

0.0000560

AC:

AN:

17846

American (AMR)

AF:

0.000182

AC:

AN:

5488

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9360

East Asian (EAS)

AF:

0.00

AC:

AN:

17094

South Asian (SAS)

AF:

0.00

AC:

AN:

18620

European-Finnish (FIN)

AF:

0.00

AC:

AN:

16320

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2768

European-Non Finnish (NFE)

AF:

0.0000469

AC:

AN:

789326

Other (OTH)

AF:

0.0000296

AC:

AN:

33818

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

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:

0.0000826

AC:

AN:

145352

Hom.:

Cov.:

AF XY:

0.0000566

AC XY:

AN XY:

70724

show subpopulations

African (AFR)

AF:

0.0000745

AC:

AN:

40264

American (AMR)

AF:

0.00

AC:

AN:

14770

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3392

East Asian (EAS)

AF:

0.00

AC:

AN:

4824

South Asian (SAS)

AF:

0.00

AC:

AN:

4708

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8524

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.000137

AC:

AN:

65702

Other (OTH)

AF:

0.00

AC:

AN:

1990

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

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:

0.0000843

Hom.:

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

Uncertain

0.38

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.00033

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.39

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

PhyloP100

0.92

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.21

REVEL

Benign

0.055

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.21

Vest4

0.17

MutPred

0.25

Loss of relative solvent accessibility (P = 0.0404)

MVP

0.043

MPC

1.6

ClinPred

0.16

GERP RS

1.9

PromoterAI

-0.043

Neutral

(source)

Varity_R

0.11

gMVP

0.38

Mutation Taster

=95/5

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