rs1085307880
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The ENST00000379644.9(HGSNAT):c.739delA(p.Arg247GlyfsTer29) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,443,546 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. R247R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
HGSNAT
ENST00000379644.9 frameshift
ENST00000379644.9 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.460
Publications
0 publications found
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 3Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health
- mucopolysaccharidosis type 3CInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Genomics England PanelApp, Ambry Genetics, G2P
- retinitis pigmentosa 73Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
- retinitis pigmentosaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 18 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 8-43170689-CA-C is Pathogenic according to our data. Variant chr8-43170689-CA-C is described in ClinVar as Pathogenic. ClinVar VariationId is 426971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: ENST00000379644.9. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| HGSNAT | NM_152419.3 | MANE Select | c.739delA | p.Arg247GlyfsTer29 | frameshift | Exon 7 of 18 | NP_689632.2 | ||
| HGSNAT | NM_001363227.2 | c.739delA | p.Arg247GlyfsTer29 | frameshift | Exon 7 of 19 | NP_001350156.1 | |||
| HGSNAT | NM_001363228.2 | c.739delA | p.Arg247GlyfsTer44 | frameshift | Exon 7 of 16 | NP_001350157.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| HGSNAT | ENST00000379644.9 | TSL:2 MANE Select | c.739delA | p.Arg247GlyfsTer29 | frameshift | Exon 7 of 18 | ENSP00000368965.4 | ||
| HGSNAT | ENST00000520704.1 | TSL:1 | n.*188delA | non_coding_transcript_exon | Exon 8 of 10 | ENSP00000429109.1 | |||
| HGSNAT | ENST00000520704.1 | TSL:1 | n.*188delA | 3_prime_UTR | Exon 8 of 10 | ENSP00000429109.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000139 AC: 2AN: 1443546Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1AN XY: 716776 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1443546
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
716776
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33096
American (AMR)
AF:
AC:
0
AN:
41996
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25636
East Asian (EAS)
AF:
AC:
0
AN:
39156
South Asian (SAS)
AF:
AC:
0
AN:
83454
European-Finnish (FIN)
AF:
AC:
0
AN:
51308
Middle Eastern (MID)
AF:
AC:
0
AN:
5730
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1103432
Other (OTH)
AF:
AC:
0
AN:
59738
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
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2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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<30
30-35
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions as Germline
Significance:Pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
2
-
-
Mucopolysaccharidosis, MPS-III-C (2)
1
-
-
Mucopolysaccharidosis, MPS-III-C;C4225287:Retinitis pigmentosa 73 (1)
1
-
-
not provided (1)
1
-
-
Sanfilippo syndrome (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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