rs17603428

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_152419.3(HGSNAT):c.1377+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 1,590,104 control chromosomes in the GnomAD database, including 82,815 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5809 hom., cov: 32)

Exomes 𝑓: 0.32 ( 77006 hom. )

Consequence

HGSNAT
NM_152419.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -2.91

Publications

7 publications found

Variant links:

Genes affected

HGSNAT (HGNC:26527): (heparan-alpha-glucosaminide N-acetyltransferase) This gene encodes a lysosomal acetyltransferase, which is one of several enzymes involved in the lysosomal degradation of heparin sulfate. Mutations in this gene are associated with Sanfilippo syndrome C, one type of the lysosomal storage disease mucopolysaccaridosis III, which results from impaired degradation of heparan sulfate. [provided by RefSeq, Jan 2009]

HGSNAT Gene-Disease associations (from GenCC):

mucopolysaccharidosis type 3
Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health
mucopolysaccharidosis type 3C
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Genomics England PanelApp, Ambry Genetics, G2P
retinitis pigmentosa 73
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

HGSNAT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 8-43192450-G-A is Benign according to our data. Variant chr8-43192450-G-A is described in ClinVar as Benign. ClinVar VariationId is 96501.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HGSNAT	NM_152419.3 link	c.1377+20G>A		intron_variant	Intron 13 of 17	ENST00000379644.9	NP_689632.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
HGSNAT	ENST00000379644.9 link	c.1377+20G>A	intron_variant	Intron 13 of 17	2	NM_152419.3	ENSP00000368965.4
HGSNAT	ENST00000521576.1 link	c.528+20G>A	intron_variant	Intron 4 of 8	2		ENSP00000429029.1
HGSNAT	ENST00000524016.5 link	c.480+20G>A	intron_variant	Intron 4 of 6	4		ENSP00000428322.1
HGSNAT	ENST00000520678.1 link	n.310+20G>A	intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.247

AC:

37546

AN:

151970

Hom.:

5808

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0591

Gnomad AMI

AF:

0.307

Gnomad AMR

AF:

0.225

Gnomad ASJ

AF:

0.387

Gnomad EAS

AF:

0.240

Gnomad SAS

AF:

0.357

Gnomad FIN

AF:

0.341

Gnomad MID

AF:

0.363

Gnomad NFE

AF:

0.335

Gnomad OTH

AF:

0.275

GnomAD2 exomes

AF:

0.300

AC:

69978

AN:

232898

AF XY:

0.312

show subpopulations

Gnomad AFR exome

AF:

0.0529

Gnomad AMR exome

AF:

0.207

Gnomad ASJ exome

AF:

0.412

Gnomad EAS exome

AF:

0.225

Gnomad FIN exome

AF:

0.336

Gnomad NFE exome

AF:

0.340

Gnomad OTH exome

AF:

0.320

GnomAD4 exome

AF:

0.322

AC:

462977

AN:

1438016

Hom.:

77006

Cov.:

AF XY:

0.324

AC XY:

231368

AN XY:

713044

show subpopulations

African (AFR)

AF:

0.0517

AC:

1688

AN:

32668

American (AMR)

AF:

0.206

AC:

8527

AN:

41490

Ashkenazi Jewish (ASJ)

AF:

0.401

AC:

10064

AN:

25086

East Asian (EAS)

AF:

0.304

AC:

11910

AN:

39238

South Asian (SAS)

AF:

0.365

AC:

30144

AN:

82628

European-Finnish (FIN)

AF:

0.338

AC:

17704

AN:

52326

Middle Eastern (MID)

AF:

0.332

AC:

1881

AN:

5658

European-Non Finnish (NFE)

AF:

0.330

AC:

362937

AN:

1099528

Other (OTH)

AF:

0.305

AC:

18122

AN:

59394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

14063

28126

42190

56253

70316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11646

23292

34938

46584

58230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.247

AC:

37551

AN:

152088

Hom.:

5809

Cov.:

AF XY:

0.248

AC XY:

18453

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.0589

AC:

2448

AN:

41540

American (AMR)

AF:

0.226

AC:

3449

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.387

AC:

1342

AN:

3468

East Asian (EAS)

AF:

0.241

AC:

1247

AN:

5166

South Asian (SAS)

AF:

0.358

AC:

1725

AN:

4820

European-Finnish (FIN)

AF:

0.341

AC:

3598

AN:

10552

Middle Eastern (MID)

AF:

0.373

AC:

109

AN:

292

European-Non Finnish (NFE)

AF:

0.335

AC:

22778

AN:

67948

Other (OTH)

AF:

0.273

AC:

576

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1357

2714

4071

5428

6785

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

406

812

1218

1624

2030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.298

Hom.:

3126

Bravo

AF:

0.229

Asia WGS

AF:

0.248

AC:

860

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Jun 03, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:4

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 26, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Dec 04, 2016

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant summary: The c.1377+20G>A in HGSNAT gene is an intronic change that involves a non-conserved nucleotide. 4/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in control population dataset of ExAC at a frequency of 0.307 (35414/115280 chrs tested). The observed frequency exceeds the estimated maximal expected allele frequency of a pathogenic variant in HGSNAT gene (0.001). The variant has been reported as Benign by a reputable database/clinical laboratory. Taking together, the variant was classified as Benign. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mucopolysaccharidosis, MPS-III-C

Benign:2

May 31, 2017

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mucopolysaccharidosis, MPS-III-C;C4225287:Retinitis pigmentosa 73

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Retinitis pigmentosa 73

Benign:1

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.010

(source)

DANN

Benign

0.38

PhyloP100

-2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over