Variant 2-128267894-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_004807.3(HS6ST1):c.*268G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0052 in 141,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0052 ( 0 hom., cov: 36)

Exomes 𝑓: 0.0030 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HS6ST1
NM_004807.3 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.844

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 2-128267894-C-G is Benign according to our data. Variant chr2-128267894-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1216882.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS6ST1	NM_004807.3 link	c.*268G>C		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.*268G>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_004807.3	ENSP00000259241.6		O60243-1
HS6ST1	ENST00000469019.1 link	n.361-21369G>C		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes

AF:

0.00520

AC:

735

AN:

141240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00299

Gnomad AMI

AF:

0.00579

Gnomad AMR

AF:

0.00391

Gnomad ASJ

AF:

0.00743

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00233

Gnomad FIN

AF:

0.0125

Gnomad MID

AF:

0.00342

Gnomad NFE

AF:

0.00639

Gnomad OTH

AF:

0.00414

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00303

AC:

1224

AN:

403624

Hom.:

Cov.:

AF XY:

0.00296

AC XY:

626

AN XY:

211354

show subpopulations

Gnomad4 AFR exome

AF:

0.000849

Gnomad4 AMR exome

AF:

0.00116

Gnomad4 ASJ exome

AF:

0.00327

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00142

Gnomad4 FIN exome

AF:

0.00403

Gnomad4 NFE exome

AF:

0.00385

Gnomad4 OTH exome

AF:

0.00278

GnomAD4 genome

AF:

0.00520

AC:

735

AN:

141360

Hom.:

Cov.:

AF XY:

0.00559

AC XY:

388

AN XY:

69378

show subpopulations

Gnomad4 AFR

AF:

0.00298

Gnomad4 AMR

AF:

0.00391

Gnomad4 ASJ

AF:

0.00743

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00233

Gnomad4 FIN

AF:

0.0125

Gnomad4 NFE

AF:

0.00639

Gnomad4 OTH

AF:

0.00409

Alfa

AF:

0.0186

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

Apr 24, 2019

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

-0.90

CADD

Benign

1.2

DANN

Benign

0.59

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