rs72647302

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.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

Publications

2 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=-0.88).

BP6

Variant 8-43159090-G-T is Benign according to our data. Variant chr8-43159090-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 262647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-43159090-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 262647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-43159090-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 262647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-43159090-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 262647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-43159090-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 262647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-43159090-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 262647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-43159090-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 262647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-43159090-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 262647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-43159090-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 262647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-43159090-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 262647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-43159090-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 262647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-43159090-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 262647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-43159090-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 262647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-43159090-G-T is described in CliVar as Benign/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 rank	MANE	Protein	UniProt
HGSNAT	NM_152419.3 link	c.493+46G>T		intron_variant	Intron 4 of 17	ENST00000379644.9	NP_689632.2	Q68CP4-2Q8IVU6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
HGSNAT	ENST00000379644.9 link	c.493+46G>T	intron_variant	Intron 4 of 17	2	NM_152419.3	ENSP00000368965.4	Q68CP4-2
HGSNAT	ENST00000520704.1 link	n.343+46G>T	intron_variant	Intron 4 of 9	1		ENSP00000429109.1	E5RJC4
HGSNAT	ENST00000517319.1 link	n.*62+46G>T	intron_variant	Intron 3 of 4	4		ENSP00000430032.1	E5RH11

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

GnomAD2 exomes

AF:

0.0324

AC:

7662

AN:

236598

AF XY:

0.0327

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 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

African (AFR)

AF:

0.00750

AC:

244

AN:

32532

American (AMR)

AF:

0.0277

AC:

1153

AN:

41584

Ashkenazi Jewish (ASJ)

AF:

0.0202

AC:

516

AN:

25578

East Asian (EAS)

AF:

0.00128

AC:

AN:

38998

South Asian (SAS)

AF:

0.0134

AC:

1102

AN:

81966

European-Finnish (FIN)

AF:

0.0308

AC:

1623

AN:

52692

Middle Eastern (MID)

AF:

0.0127

AC:

AN:

5664

European-Non Finnish (NFE)

AF:

0.0566

AC:

62064

AN:

1096290

Other (OTH)

AF:

0.0425

AC:

2511

AN:

59070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

2859

5718

8578

11437

14296

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2378

4756

7134

9512

11890

<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:

0.0331

AC:

5032

AN:

152140

Hom.:

115

Cov.:

AF XY:

0.0313

AC XY:

2328

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.00961

AC:

399

AN:

41524

American (AMR)

AF:

0.0372

AC:

568

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.0248

AC:

AN:

3468

East Asian (EAS)

AF:

0.000386

AC:

AN:

5178

South Asian (SAS)

AF:

0.0112

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.0313

AC:

331

AN:

10580

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0516

AC:

3511

AN:

67990

Other (OTH)

AF:

0.0256

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

235

471

706

942

1177

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<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:

0.0451

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

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 31, 2017

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Oct 17, 2018

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.17

(source)

DANN

Benign

0.54

PhyloP100

-1.2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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