dbSNP rs561805580: HS3ST2:p.Thr79Lys (chr16-22814846-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006043.2(HS3ST2):c.236C>A(p.Thr79Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000212 in 1,413,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. T79M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

HS3ST2
NM_006043.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.629

Publications

1 publications found

Variant links:

Genes affected

HS3ST2 (HGNC:5195): (heparan sulfate-glucosamine 3-sulfotransferase 2) Heparan sulfate biosynthetic enzymes are key components in generating a myriad of distinct heparan sulfate fine structures that carry out multiple biologic activities. The enzyme encoded by this gene is a member of the heparan sulfate biosynthetic enzyme family. It is a type II integral membrane protein and possesses heparan sulfate glucosaminyl 3-O-sulfotransferase activity. This gene is expressed predominantly in brain and may play a role in the nervous system. [provided by RefSeq, Jul 2008]

HS3ST2 links:

ENSG00000283213 (HGNC:):

ENSG00000283213 links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05670768).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006043.2. 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
	HS3ST2	NM_006043.2	MANE Select	c.236C>A	p.Thr79Lys	missense	Exon 1 of 2	NP_006034.1	Q9Y278

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HS3ST2	ENST00000261374.4	TSL:1 MANE Select	c.236C>A	p.Thr79Lys	missense	Exon 1 of 2	ENSP00000261374.3	Q9Y278
HS3ST2	ENST00000473392.1	TSL:5	n.236C>A		non_coding_transcript_exon	Exon 1 of 4	ENSP00000454505.1	H3BMR2
ENSG00000283213	ENST00000804050.1		n.14G>T		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000622

AC:

AN:

160698

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000212

AC:

AN:

1413180

Hom.:

Cov.:

AF XY:

0.00000286

AC XY:

AN XY:

698548

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32234

American (AMR)

AF:

0.00

AC:

AN:

37570

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25238

East Asian (EAS)

AF:

0.00

AC:

AN:

36850

South Asian (SAS)

AF:

0.0000246

AC:

AN:

81144

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48148

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

9.19e-7

AC:

AN:

1087858

Other (OTH)

AF:

0.00

AC:

AN:

58452

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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.038

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.44

M_CAP

Benign

0.044

MetaRNN

Benign

0.057

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

0.63

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.41

REVEL

Benign

0.12

Sift

Benign

0.87

Sift4G

Benign

0.90

Polyphen

0.0020

Vest4

0.16

MutPred

0.30

Gain of methylation at T79 (P = 0.004)

MVP

0.22

MPC

1.2

ClinPred

0.092

GERP RS

1.3

Varity_R

0.083

gMVP

0.51

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