rs17603428

Positions:

chr8-43192450-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 links:

HGSNAT (HGNC:):

HGSNAT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 96501.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-43192450-G-A is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
HGSNAT	NM_152419.3 linkuse as main transcript	c.1377+20G>A		intron_variant		ENST00000379644.9	NP_689632.2	Q68CP4-2Q8IVU6

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
HGSNAT	ENST00000379644.9 linkuse as main transcript	c.1377+20G>A	intron_variant	2	NM_152419.3	ENSP00000368965.4	Q68CP4-2
HGSNAT	ENST00000521576.1 linkuse as main transcript	c.528+20G>A	intron_variant	2		ENSP00000429029.1	E5RJN0
HGSNAT	ENST00000524016.5 linkuse as main transcript	c.480+20G>A	intron_variant	4		ENSP00000428322.1	H0YAZ0
HGSNAT	ENST00000520678.1 linkuse as main transcript	n.310+20G>A	intron_variant	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

GnomAD3 exomes

AF:

0.300

AC:

69978

AN:

232898

Hom.:

11312

AF XY:

0.312

AC XY:

39332

AN XY:

126264

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 SAS exome

AF:

0.369

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

Gnomad4 AFR exome

AF:

0.0517

Gnomad4 AMR exome

AF:

0.206

Gnomad4 ASJ exome

AF:

0.401

Gnomad4 EAS exome

AF:

0.304

Gnomad4 SAS exome

AF:

0.365

Gnomad4 FIN exome

AF:

0.338

Gnomad4 NFE exome

AF:

0.330

Gnomad4 OTH exome

AF:

0.305

GnomAD4 genome

AF:

0.247

AC:

37551

AN:

152088

Hom.:

5809

Cov.:

AF XY:

0.248

AC XY:

18453

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.0589

Gnomad4 AMR

AF:

0.226

Gnomad4 ASJ

AF:

0.387

Gnomad4 EAS

AF:

0.241

Gnomad4 SAS

AF:

0.358

Gnomad4 FIN

AF:

0.341

Gnomad4 NFE

AF:

0.335

Gnomad4 OTH

AF:

0.273

Alfa

AF:

0.308

Hom.:

2075

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

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 03, 2014	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:4

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 26, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 04, 2016	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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Mucopolysaccharidosis, MPS-III-C

Benign:2

Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	May 31, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Retinitis pigmentosa 73

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.010

DANN

Benign

0.38

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