Variant 2-128267822-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_004807.3(HS6ST1):c.*340C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00616 in 404,498 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0061 ( 1 hom., cov: 35)

Exomes 𝑓: 0.0062 ( 9 hom. )

Consequence

HS6ST1
NM_004807.3 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.27

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 2-128267822-G-A is Benign according to our data. Variant chr2-128267822-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1197915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 9 AD,AR,Digenic,Multigenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS6ST1	NM_004807.3 link	c.*340C>T		3_prime_UTR_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 link	c.*340C>T		3_prime_UTR_variant	Exon 2 of 2	1	NM_004807.3	ENSP00000259241.6		O60243-1
HS6ST1	ENST00000469019.1 link	n.361-21297C>T		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes

AF:

0.00614

AC:

899

AN:

146424

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00328

Gnomad AMI

AF:

0.0165

Gnomad AMR

AF:

0.00698

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.0104

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00709

Gnomad OTH

AF:

0.00732

GnomAD4 exome

AF:

0.00617

AC:

1591

AN:

257968

Hom.:

Cov.:

AF XY:

0.00570

AC XY:

763

AN XY:

133884

show subpopulations

Gnomad4 AFR exome

AF:

0.00139

Gnomad4 AMR exome

AF:

0.00668

Gnomad4 ASJ exome

AF:

0.0108

Gnomad4 EAS exome

AF:

0.00205

Gnomad4 SAS exome

AF:

0.000411

Gnomad4 FIN exome

AF:

0.0112

Gnomad4 NFE exome

AF:

0.00707

Gnomad4 OTH exome

AF:

0.00686

GnomAD4 genome

AF:

0.00615

AC:

901

AN:

146530

Hom.:

Cov.:

AF XY:

0.00636

AC XY:

456

AN XY:

71706

show subpopulations

Gnomad4 AFR

AF:

0.00333

Gnomad4 AMR

AF:

0.00697

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0104

Gnomad4 NFE

AF:

0.00709

Gnomad4 OTH

AF:

0.00725

Alfa

AF:

0.00710

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 20, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.85

DANN

Benign

0.53

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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