Variant 16-22814920-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006043.2(HS3ST2):c.310T>C(p.Ser104Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000918 in 1,599,774 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00095 ( 3 hom. )

Consequence

HS3ST2
NM_006043.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.356

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.020277262).

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HS3ST2	NM_006043.2 linkuse as main transcript	c.310T>C	p.Ser104Pro	missense_variant	1/2	ENST00000261374.4	NP_006034.1	Q9Y278
HS3ST2	XM_011546001.4 linkuse as main transcript	c.310T>C	p.Ser104Pro	missense_variant	1/2		XP_011544303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HS3ST2	ENST00000261374.4 linkuse as main transcript	c.310T>C	p.Ser104Pro	missense_variant	1/2	1	NM_006043.2	ENSP00000261374.3		Q9Y278
HS3ST2	ENST00000473392.1 linkuse as main transcript	n.310T>C		non_coding_transcript_exon_variant	1/4	5		ENSP00000454505.1		H3BMR2

Frequencies

GnomAD3 genomes

AF:

0.000565

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

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:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00116

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000364

AC:

AN:

219864

Hom.:

AF XY:

0.000374

AC XY:

AN XY:

120442

show subpopulations

Gnomad AFR exome

AF:

0.000244

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000517

Gnomad NFE exome

AF:

0.000785

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000955

AC:

1382

AN:

1447480

Hom.:

Cov.:

AF XY:

0.000927

AC XY:

666

AN XY:

718782

show subpopulations

Gnomad4 AFR exome

AF:

0.000151

Gnomad4 AMR exome

AF:

0.0000233

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000234

Gnomad4 NFE exome

AF:

0.00115

Gnomad4 OTH exome

AF:

0.00161

GnomAD4 genome

AF:

0.000565

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.000577

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00116

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000745

Hom.:

Bravo

AF:

0.000574

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000232

AC:

ESP6500EA

AF:

0.000586

AC:

ExAC

AF:

0.000265

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 17, 2023

The c.310T>C (p.S104P) alteration is located in exon 1 (coding exon 1) of the HS3ST2 gene. This alteration results from a T to C substitution at nucleotide position 310, causing the serine (S) at amino acid position 104 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.054

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.47

M_CAP

Benign

0.044

MetaRNN

Benign

0.020

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.96

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.95

REVEL

Benign

0.085

Sift

Uncertain

0.025

Sift4G

Benign

0.24

Polyphen

0.0040

Vest4

0.075

MVP

0.53

MPC

1.3

ClinPred

0.021

GERP RS

3.8

Varity_R

0.26

gMVP

0.62

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over