8-43197696-A-C

Position:

chr8-43197696-A-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_152419.3(HGSNAT):c.1567A>C(p.Lys523Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00608 in 1,613,202 control chromosomes in the GnomAD database, including 550 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 305 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 245 hom. )

Consequence

HGSNAT
NM_152419.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 4.17

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 -16 ACMG points.

BP6

Variant 8-43197696-A-C is Benign according to our data. Variant chr8-43197696-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 363150.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-43197696-A-C is described in Lovd as [Benign]. Variant chr8-43197696-A-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.115 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.1567A>C	p.Lys523Gln	missense_variant	16/18	ENST00000379644.9	NP_689632.2	Q68CP4-2Q8IVU6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HGSNAT	ENST00000379644.9 linkuse as main transcript	c.1567A>C	p.Lys523Gln	missense_variant	16/18	2	NM_152419.3	ENSP00000368965.4	Q68CP4-2
HGSNAT	ENST00000519705.1 linkuse as main transcript	n.883A>C		non_coding_transcript_exon_variant	2/4	1
HGSNAT	ENST00000521576.1 linkuse as main transcript	c.718A>C	p.Lys240Gln	missense_variant	7/9	2		ENSP00000429029.1	E5RJN0
HGSNAT	ENST00000523989.1 linkuse as main transcript	n.1880A>C		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes

AF:

0.0335

AC:

5096

AN:

152090

Hom.:

304

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00982

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.0172

GnomAD3 exomes

AF:

0.00856

AC:

2134

AN:

249284

Hom.:

107

AF XY:

0.00656

AC XY:

887

AN XY:

135234

show subpopulations

Gnomad AFR exome

AF:

0.124

Gnomad AMR exome

AF:

0.00461

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.00446

GnomAD4 exome

AF:

0.00322

AC:

4706

AN:

1460994

Hom.:

245

Cov.:

AF XY:

0.00276

AC XY:

2006

AN XY:

726858

show subpopulations

Gnomad4 AFR exome

AF:

0.119

Gnomad4 AMR exome

AF:

0.00521

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000909

Gnomad4 OTH exome

AF:

0.00641

GnomAD4 genome

AF:

0.0335

AC:

5104

AN:

152208

Hom.:

305

Cov.:

AF XY:

0.0328

AC XY:

2441

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.118

Gnomad4 AMR

AF:

0.00981

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.0170

Alfa

AF:

0.00530

Hom.:

Bravo

AF:

0.0372

ESP6500AA

AF:

0.114

AC:

418

ESP6500EA

AF:

0.000245

AC:

ExAC

AF:

0.0106

AC:

1284

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Sep 21, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 31, 2018	This variant is associated with the following publications: (PMID: 17033958, 21228398, 19823584, 20981092, 19479962, 20583299) -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 05, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Oct 11, 2021	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Mucopolysaccharidosis, MPS-III-C

Benign:2

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Benign

0.96

Eigen

Benign

0.13

Eigen_PC

Benign

0.036

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.80

T;T

MetaRNN

Benign

0.0025

T;T

MetaSVM

Benign

-0.88

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.6

N;N

REVEL

Uncertain

0.45

Sift

Benign

0.066

T;T

Sift4G

Benign

0.43

T;T

Vest4

0.42

MPC

0.15

ClinPred

0.035

GERP RS

4.3

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.32

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.32

Position offset: 3

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