2-128267829-TC-T

Variant names:

• chr2-128267829-TC-T
• rs58484518
• NM_004807.3:c.*332delG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004807.3(HS6ST1):​c.*332delG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0641 in 440,932 control chromosomes in the GnomAD database, including 2,993 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (2248 hom., cov: 34)
  • Exomes 𝑓: 0.038 (745 hom.)
• Consequence: HS6ST1 NM_004807.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0170

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-128267829-TC-T is Benign according to our data. Variant chr2-128267829-TC-T is described in ClinVar as [Benign]. Clinvar id is 1225191.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS6ST1	NM_004807.3	c.*332delG		3_prime_UTR_variant	Exon 2 of 2	ENST00000259241.7	NP_004798.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HS6ST1	ENST00000259241	c.*332delG		3_prime_UTR_variant	Exon 2 of 2	1	NM_004807.3	ENSP00000259241.6
HS6ST1	ENST00000469019.1	n.361-21305delG		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17285 AN: 151606 Hom.: 2242 Cov.: 34

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0537

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0383

Gnomad FIN AF: 0.0159

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0276

Gnomad OTH AF: 0.0967

GnomAD4 exome AF: 0.0379 AC: 10969 AN: 289208 Hom.: 745 Cov.: 0 AF XY: 0.0365 AC XY: 5486 AN XY: 150412

Gnomad4 AFR exome AF: 0.350

Gnomad4 AMR exome AF: 0.0372

Gnomad4 ASJ exome AF: 0.0318

Gnomad4 EAS exome AF: 0.0000530

Gnomad4 SAS exome AF: 0.0356

Gnomad4 FIN exome AF: 0.0155

Gnomad4 NFE exome AF: 0.0275

Gnomad4 OTH exome AF: 0.0458

GnomAD4 genome AF: 0.114 AC: 17314 AN: 151724 Hom.: 2248 Cov.: 34 AF XY: 0.111 AC XY: 8217 AN XY: 74230

Gnomad4 AFR AF: 0.339

Gnomad4 AMR AF: 0.0536

Gnomad4 ASJ AF: 0.0389

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0379

Gnomad4 FIN AF: 0.0159

Gnomad4 NFE AF: 0.0276

Gnomad4 OTH AF: 0.0961

Alfa AF: 0.00907 Hom.: 2

Asia WGS AF: 0.0300 AC: 105 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 24, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs58484518; hg19: chr2-129025403;