Variant chr8-43159090-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_152419.3(HGSNAT):c.493+46G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0469 in 1,586,514 control chromosomes in the GnomAD database, including 2,060 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 115 hom., cov: 32)

Exomes 𝑓: 0.048 ( 1945 hom. )

Consequence

HGSNAT
NM_152419.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.23

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:

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=-0.88).

BP6

Variant 8-43159090-G-T is Benign according to our data. Variant chr8-43159090-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 262647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0502 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.493+46G>T		intron_variant		ENST00000379644.9	NP_689632.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
HGSNAT	ENST00000379644.9 linkuse as main transcript	c.493+46G>T	intron_variant	2	NM_152419.3	ENSP00000368965	P3	Q68CP4-2
HGSNAT	ENST00000520704.1 linkuse as main transcript	c.343+46G>T	intron_variant, NMD_transcript_variant	1		ENSP00000429109
HGSNAT	ENST00000517319.1 linkuse as main transcript	c.*62+46G>T	intron_variant, NMD_transcript_variant	4		ENSP00000430032

Frequencies

GnomAD3 genomes

AF:

0.0331

AC:

5032

AN:

152022

Hom.:

115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00964

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0373

Gnomad ASJ

AF:

0.0248

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0112

Gnomad FIN

AF:

0.0313

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0516

Gnomad OTH

AF:

0.0258

GnomAD3 exomes

AF:

0.0324

AC:

7662

AN:

236598

Hom.:

166

AF XY:

0.0327

AC XY:

4202

AN XY:

128378

show subpopulations

Gnomad AFR exome

AF:

0.00867

Gnomad AMR exome

AF:

0.0258

Gnomad ASJ exome

AF:

0.0223

Gnomad EAS exome

AF:

0.000404

Gnomad SAS exome

AF:

0.0118

Gnomad FIN exome

AF:

0.0301

Gnomad NFE exome

AF:

0.0488

Gnomad OTH exome

AF:

0.0414

GnomAD4 exome

AF:

0.0483

AC:

69335

AN:

1434374

Hom.:

1945

Cov.:

AF XY:

0.0476

AC XY:

33815

AN XY:

710990

show subpopulations

Gnomad4 AFR exome

AF:

0.00750

Gnomad4 AMR exome

AF:

0.0277

Gnomad4 ASJ exome

AF:

0.0202

Gnomad4 EAS exome

AF:

0.00128

Gnomad4 SAS exome

AF:

0.0134

Gnomad4 FIN exome

AF:

0.0308

Gnomad4 NFE exome

AF:

0.0566

Gnomad4 OTH exome

AF:

0.0425

GnomAD4 genome

AF:

0.0331

AC:

5032

AN:

152140

Hom.:

115

Cov.:

AF XY:

0.0313

AC XY:

2328

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.00961

Gnomad4 AMR

AF:

0.0372

Gnomad4 ASJ

AF:

0.0248

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0112

Gnomad4 FIN

AF:

0.0313

Gnomad4 NFE

AF:

0.0516

Gnomad4 OTH

AF:

0.0256

Alfa

AF:

0.0424

Hom.:

Bravo

AF:

0.0330

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 31, 2017	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 17, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.17

DANN

Benign

0.54

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