Genetic Variant HS3ST5:p.Arg325His (chr6-114057324-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_153612.4(HS3ST5):c.974G>A(p.Arg325His) variant causes a missense change. The variant allele was found at a frequency of 0.0000533 in 1,613,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000052 ( 0 hom. )

Consequence

HS3ST5
NM_153612.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.88

Publications

3 publications found

Variant links:

Genes affected

HS3ST5 (HGNC:19419): (heparan sulfate-glucosamine 3-sulfotransferase 5) HS3ST5 belongs to a group of heparan sulfate 3-O-sulfotransferases (EC 2.8.2.23) that transfer sulfate from 3-prime-phosphoadenosine 5-prime phosphosulfate (PAPS) to heparan sulfate and heparin (Mochizuki et al., 2003 [PubMed 12740361]).[supplied by OMIM, Mar 2008]

HS3ST5 links:

HDAC2-AS2 (HGNC:43590): (HDAC2 and HS3ST5 antisense RNA 2)

HDAC2-AS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1052731).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153612.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HS3ST5	NM_153612.4	MANE Select	c.974G>A	p.Arg325His	missense	Exon 5 of 5	NP_705840.2
HS3ST5	NM_001387039.1		c.974G>A	p.Arg325His	missense	Exon 4 of 4	NP_001373968.1	Q8IZT8
HS3ST5	NM_001387040.1		c.974G>A	p.Arg325His	missense	Exon 3 of 3	NP_001373969.1	Q8IZT8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HS3ST5	ENST00000312719.10	TSL:2 MANE Select	c.974G>A	p.Arg325His	missense	Exon 5 of 5	ENSP00000427888.1	Q8IZT8
HDAC2-AS2	ENST00000519104.5	TSL:1	n.1311-31613C>T		intron	N/A
HS3ST5	ENST00000900060.1		c.974G>A	p.Arg325His	missense	Exon 6 of 6	ENSP00000570119.1

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000478

AC:

AN:

250858

AF XY:

0.0000516

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000520

AC:

AN:

1461758

Hom.:

Cov.:

AF XY:

0.0000619

AC XY:

AN XY:

727164

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000209

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.0000562

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000432

AC:

AN:

1111960

Other (OTH)

AF:

0.0000331

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

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:

0.0000658

AC:

AN:

152070

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.0000966

AC:

AN:

41396

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00104

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

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:

0.0000434

Hom.:

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

0.10

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.36

Eigen

Benign

0.0043

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.015

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.76

MutationAssessor

Benign

1.7

PhyloP100

3.9

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.5

REVEL

Uncertain

0.33

Sift

Benign

0.37

Sift4G

Benign

0.46

Polyphen

0.0050

Vest4

0.090

MVP

0.25

MPC

0.27

ClinPred

0.12

GERP RS

6.0

Varity_R

0.21

gMVP

0.58

Mutation Taster

=47/53

disease causing

(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