NM_000263.4:c.1444C>A
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_000263.4(NAGLU):c.1444C>A(p.Arg482Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,445,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. R482R) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
NAGLU
NM_000263.4 synonymous
NM_000263.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.26
Publications
13 publications found
Genes affected
NAGLU (HGNC:7632): (N-acetyl-alpha-glucosaminidase) This gene encodes an enzyme that degrades heparan sulfate by hydrolysis of terminal N-acetyl-D-glucosamine residues in N-acetyl-alpha-D-glucosaminides. Defects in this gene are the cause of mucopolysaccharidosis type IIIB (MPS-IIIB), also known as Sanfilippo syndrome B. This disease is characterized by the lysosomal accumulation and urinary excretion of heparan sulfate. [provided by RefSeq, Jul 2008]
NAGLU Gene-Disease associations (from GenCC):
- mucopolysaccharidosis type 3BInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Orphanet, Myriad Women’s Health
- Charcot-Marie-Tooth disease axonal type 2VInheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
Variant 17-42543450-C-A is Benign according to our data. Variant chr17-42543450-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2950437.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=2.26 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000263.4. 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 |
|---|---|---|---|---|---|---|---|---|---|
| NAGLU | NM_000263.4 | MANE Select | c.1444C>A | p.Arg482Arg | synonymous | Exon 6 of 6 | NP_000254.2 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| NAGLU | ENST00000225927.7 | TSL:1 MANE Select | c.1444C>A | p.Arg482Arg | synonymous | Exon 6 of 6 | ENSP00000225927.1 | ||
| NAGLU | ENST00000591587.1 | TSL:5 | c.*413C>A | 3_prime_UTR | Exon 4 of 4 | ENSP00000467836.1 | |||
| NAGLU | ENST00000592454.1 | TSL:2 | c.*287C>A | 3_prime_UTR | Exon 2 of 2 | ENSP00000468665.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000138 AC: 2AN: 1445870Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1AN XY: 718458 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
2
AN:
1445870
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
718458
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33242
American (AMR)
AF:
AC:
0
AN:
42608
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25842
East Asian (EAS)
AF:
AC:
0
AN:
38964
South Asian (SAS)
AF:
AC:
0
AN:
84694
European-Finnish (FIN)
AF:
AC:
0
AN:
49040
Middle Eastern (MID)
AF:
AC:
0
AN:
5752
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1105958
Other (OTH)
AF:
AC:
0
AN:
59770
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00666416), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.325
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<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
GnomAD4 genome
Cov.:
33
Alfa
AF:
Hom.:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Mucopolysaccharidosis, MPS-III-B;C5569050:Charcot-Marie-Tooth disease axonal type 2V Benign:1
Jul 31, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
RBP_binding_hub_radar
RBP_regulation_power_radar
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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