Genetic Variant HS3ST4:p.Pro114Leu (chr16-25692758-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.341C>T(p.Pro114Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HS3ST4
NM_006040.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.566

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:

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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=0.1102559).

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.341C>T	p.Pro114Leu	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.341C>T	p.Pro114Leu	missense	Exon 1 of 2	ENSP00000330606.5	Q9Y661
ENSG00000310159	ENST00000847723.1		n.-57G>A		upstream_gene	N/A
ENSG00000310159	ENST00000847724.1		n.-57G>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1189288

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

577228

African (AFR)

AF:

0.00

AC:

AN:

23446

American (AMR)

AF:

0.00

AC:

AN:

11336

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16924

East Asian (EAS)

AF:

0.00

AC:

AN:

26714

South Asian (SAS)

AF:

0.00

AC:

AN:

44418

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28062

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3320

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

986752

Other (OTH)

AF:

0.00

AC:

AN:

48316

GnomAD4 genome

Cov.:

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

0.076

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.00035

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.51

M_CAP

Pathogenic

0.68

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.69

PhyloP100

0.57

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

0.0

REVEL

Benign

0.064

Sift

Benign

0.25

Sift4G

Benign

0.47

Polyphen

0.0

Vest4

0.053

MutPred

0.21

Loss of glycosylation at P114 (P = 0.0171)

MVP

0.043

MPC

1.6

ClinPred

0.087

GERP RS

2.4

Varity_R

0.059

gMVP

0.29

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