dbSNP rs76750342: HGSNAT:c.1727-9C>G (chr8-43199379-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_152419.3(HGSNAT):c.1727-9C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00193 in 1,566,972 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 30 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 25 hom. )

Consequence

HGSNAT
NM_152419.3 intron

Scores

Splicing: ADA: 0.001003

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0970

Publications

0 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):

inherited retinal dystrophy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
mucopolysaccharidosis type 3
Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health
mucopolysaccharidosis type 3C
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, G2P, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
retinitis pigmentosa 73
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
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=-0.8).

BP6

Variant 8-43199379-C-G is Benign according to our data. Variant chr8-43199379-C-G is described in ClinVar as Benign. ClinVar VariationId is 496837.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0106 (1613/152296) while in subpopulation AFR AF = 0.0361 (1501/41560). AF 95% confidence interval is 0.0346. There are 30 homozygotes in GnomAd4. There are 777 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 30 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152419.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
HGSNAT	NM_152419.3	MANE Select	c.1727-9C>G	intron	N/A	NP_689632.2
HGSNAT	NM_001363227.2		c.1814-9C>G	intron	N/A	NP_001350156.1
HGSNAT	NM_001363228.2		c.1535-9C>G	intron	N/A	NP_001350157.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HGSNAT	ENST00000379644.9	TSL:2 MANE Select	c.1727-9C>G	intron	N/A	ENSP00000368965.4	Q68CP4-2
HGSNAT	ENST00000519705.1	TSL:1	n.1043-9C>G	intron	N/A
HGSNAT	ENST00000902460.1		c.1928-9C>G	intron	N/A	ENSP00000572519.1

Frequencies

GnomAD3 genomes

AF:

0.0106

AC:

1611

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00530

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.00255

AC:

534

AN:

209060

AF XY:

0.00196

show subpopulations

Gnomad AFR exome

AF:

0.0368

Gnomad AMR exome

AF:

0.00167

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000763

Gnomad OTH exome

AF:

0.00113

GnomAD4 exome

AF:

0.00100

AC:

1419

AN:

1414676

Hom.:

Cov.:

AF XY:

0.000873

AC XY:

613

AN XY:

702424

show subpopulations

African (AFR)

AF:

0.0358

AC:

1163

AN:

32502

American (AMR)

AF:

0.00189

AC:

AN:

40298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25484

East Asian (EAS)

AF:

0.00

AC:

AN:

38658

South Asian (SAS)

AF:

0.0000737

AC:

AN:

81386

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51834

Middle Eastern (MID)

AF:

0.000351

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.0000519

AC:

AN:

1079976

Other (OTH)

AF:

0.00197

AC:

116

AN:

58838

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

120

181

241

301

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<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:

0.0106

AC:

1613

AN:

152296

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

777

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0361

AC:

1501

AN:

41560

American (AMR)

AF:

0.00529

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000414

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68018

Other (OTH)

AF:

0.0109

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

168

252

336

420

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00297

Hom.:

Bravo

AF:

0.0128

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Mucopolysaccharidosis, MPS-III-C (2)

Mucopolysaccharidosis, MPS-III-C;C4225287:Retinitis pigmentosa 73 (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.5

(source)

DANN

Benign

0.51

PhyloP100

0.097

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0010

dbscSNV1_RF

Benign

0.13

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over