Variant 2-128268221-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004807.3(HS6ST1):c.1177G>A(p.Asp393Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000901 in 1,609,984 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 2 hom., cov: 34)

Exomes 𝑓: 0.00083 ( 6 hom. )

Consequence

HS6ST1
NM_004807.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.80

Variant links:

Genes affected

HS6ST1 (HGNC:5201): (heparan sulfate 6-O-sulfotransferase 1) The protein encoded by this gene is a member of the heparan sulfate biosynthetic enzyme family. Heparan sulfate biosynthetic enzymes are key components in generating a myriad of distinct heparan sulfate fine structures that carry out multiple biological activities. This enzyme is a type II integral membrane protein and is responsible for 6-O-sulfation of heparan sulfate. This enzyme does not share significant sequence similarity with other known sulfotransferases. A pseudogene located on chromosome 1 has been found for this gene. [provided by RefSeq, Jul 2008]

HS6ST1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005448073).

BP6

Variant 2-128268221-C-T is Benign according to our data. Variant chr2-128268221-C-T is described in ClinVar as [Benign]. Clinvar id is 2067871.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AD,AR,Digenic,Multigenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS6ST1	NM_004807.3 link	c.1177G>A	p.Asp393Asn	missense_variant	Exon 2 of 2	ENST00000259241.7	NP_004798.3	O60243-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HS6ST1	ENST00000259241.7 link	c.1177G>A	p.Asp393Asn	missense_variant	Exon 2 of 2	1	NM_004807.3	ENSP00000259241.6		O60243-1
HS6ST1	ENST00000469019.1 link	n.361-21696G>A		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes

AF:

0.00155

AC:

236

AN:

151978

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0132

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.0139

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.00239

AC:

585

AN:

245162

Hom.:

AF XY:

0.00228

AC XY:

306

AN XY:

133966

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000873

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0122

Gnomad SAS exome

AF:

0.000688

Gnomad FIN exome

AF:

0.0139

Gnomad NFE exome

AF:

0.000381

Gnomad OTH exome

AF:

0.000842

GnomAD4 exome

AF:

0.000833

AC:

1215

AN:

1457888

Hom.:

Cov.:

AF XY:

0.000829

AC XY:

601

AN XY:

725046

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000672

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0109

Gnomad4 SAS exome

AF:

0.000488

Gnomad4 FIN exome

AF:

0.0120

Gnomad4 NFE exome

AF:

0.0000738

Gnomad4 OTH exome

AF:

0.000465

GnomAD4 genome

AF:

0.00155

AC:

236

AN:

152096

Hom.:

Cov.:

AF XY:

0.00226

AC XY:

168

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0132

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.0139

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.000475

Alfa

AF:

0.000270

Hom.:

Bravo

AF:

0.000540

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000241

AC:

ExAC

AF:

0.00202

AC:

244

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 14, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.066

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.31

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.30

MetaRNN

Benign

0.0054

MetaSVM

Benign

-0.85

MutationAssessor

Benign

-0.34

PrimateAI

Uncertain

0.62

PROVEAN

Benign

0.050

REVEL

Benign

0.21

Sift

Benign

0.11

Sift4G

Benign

0.24

Polyphen

0.082

Vest4

0.14

MVP

0.50

ClinPred

0.071

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.10

gMVP

0.13

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