Variant 13-96090993-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000376705.4(HS6ST3):c.131G>C(p.Gly44Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000846 in 1,181,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 8.5e-7 ( 0 hom. )

Consequence

HS6ST3
ENST00000376705.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.18

Variant links:

Genes affected

HS6ST3 (HGNC:19134): (heparan sulfate 6-O-sulfotransferase 3) Heparan sulfate (HS) sulfotransferases, such as HS6ST3, modify HS to generate structures required for interactions between HS and a variety of proteins. These interactions are implicated in proliferation and differentiation, adhesion, migration, inflammation, blood coagulation, and other diverse processes (Habuchi et al., 2000 [PubMed 10644753]).[supplied by OMIM, Mar 2008]

HS6ST3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18397042).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HS6ST3	NM_153456.4 linkuse as main transcript	c.131G>C	p.Gly44Ala	missense_variant	1/2	ENST00000376705.4	NP_703157.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HS6ST3	ENST00000376705.4 linkuse as main transcript	c.131G>C	p.Gly44Ala	missense_variant	1/2	1	NM_153456.4	ENSP00000365895	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000847

AC:

AN:

118036

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

66758

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000167

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

8.46e-7

AC:

AN:

1181516

Hom.:

Cov.:

AF XY:

0.00000174

AC XY:

AN XY:

575368

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000103

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000841

AC:

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

Jun 06, 2023

The c.131G>C (p.G44A) alteration is located in exon 1 (coding exon 1) of the HS6ST3 gene. This alteration results from a G to C substitution at nucleotide position 131, causing the glycine (G) at amino acid position 44 to be replaced by an alanine (A). 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

0.075

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0070

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.54

M_CAP

Pathogenic

0.83

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.74

MutationAssessor

Benign

0.81

MutationTaster

Benign

0.91

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.68

REVEL

Benign

0.13

Sift

Benign

0.12

Sift4G

Benign

0.12

Polyphen

0.0

Vest4

0.20

MutPred

0.20

Gain of catalytic residue at P48 (P = 0.0016);

MVP

0.18

MPC

0.57

ClinPred

0.16

GERP RS

2.7

Varity_R

0.14

gMVP

0.16

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