NM_004807.3:c.*332delG

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• hypogonadotropic hypogonadism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Kallmann syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hypogonadotropic hypogonadism 15 with or without anosmia

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004807.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS6ST1	NM_004807.3	MANE Select	c.*332delG		3_prime_UTR	Exon 2 of 2	NP_004798.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS6ST1	ENST00000259241.7	TSL:1 MANE Select	c.*332delG		3_prime_UTR	Exon 2 of 2	ENSP00000259241.6	O60243-1
	HS6ST1	ENST00000469019.1	TSL:4	n.361-21305delG		intron	N/A

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

African (AFR) AF: 0.350 AC: 3258 AN: 9316

American (AMR) AF: 0.0372 AC: 446 AN: 11978

Ashkenazi Jewish (ASJ) AF: 0.0318 AC: 292 AN: 9182

East Asian (EAS) AF: 0.0000530 AC: 1 AN: 18864

South Asian (SAS) AF: 0.0356 AC: 1078 AN: 30242

European-Finnish (FIN) AF: 0.0155 AC: 266 AN: 17206

Middle Eastern (MID) AF: 0.0464 AC: 62 AN: 1336

European-Non Finnish (NFE) AF: 0.0275 AC: 4790 AN: 174158

Other (OTH) AF: 0.0458 AC: 776 AN: 16926

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

African (AFR) AF: 0.339 AC: 13892 AN: 41028

American (AMR) AF: 0.0536 AC: 819 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0389 AC: 135 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0379 AC: 183 AN: 4830

European-Finnish (FIN) AF: 0.0159 AC: 169 AN: 10620

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0276 AC: 1875 AN: 68000

Other (OTH) AF: 0.0961 AC: 203 AN: 2112

Alfa AF: 0.00907 Hom.: 2

Asia WGS AF: 0.0300 AC: 105 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.017
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs58484518; hg19: chr2-129025403;