chr17-42537436-CTTT-C
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM1PM2PM4_Supporting
The NM_000263.4(NAGLU):c.423_425delTTT(p.Phe142del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00000248 in 1,614,114 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S141S) has been classified as Benign.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 35)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
NAGLU
NM_000263.4 disruptive_inframe_deletion
NM_000263.4 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.60
Publications
0 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: Uncertain_significance. The variant received 5 ACMG points.
PM1
In a hotspot region, there are 4 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 5 uncertain in NM_000263.4
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_000263.4. Strenght limited to Supporting due to length of the change: 1aa.
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.423_425delTTT | p.Phe142del | disruptive_inframe_deletion | Exon 2 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.423_425delTTT | p.Phe142del | disruptive_inframe_deletion | Exon 2 of 6 | ENSP00000225927.1 | ||
| NAGLU | ENST00000590358.1 | TSL:4 | c.111_113delTTT | p.Phe38del | disruptive_inframe_deletion | Exon 1 of 2 | ENSP00000466892.1 | ||
| NAGLU | ENST00000586516.5 | TSL:2 | c.132+782_132+784delTTT | intron | N/A | ENSP00000467135.1 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152248Hom.: 0 Cov.: 35 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152248
Hom.:
Cov.:
35
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461866Hom.: 0 AF XY: 0.00000413 AC XY: 3AN XY: 727232 show subpopulations
GnomAD4 exome
AF:
AC:
3
AN:
1461866
Hom.:
AF XY:
AC XY:
3
AN XY:
727232
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
3
AN:
1111988
Other (OTH)
AF:
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.458
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000657 AC: 1AN: 152248Hom.: 0 Cov.: 35 AF XY: 0.0000134 AC XY: 1AN XY: 74382 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152248
Hom.:
Cov.:
35
AF XY:
AC XY:
1
AN XY:
74382
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41462
American (AMR)
AF:
AC:
0
AN:
15292
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5196
South Asian (SAS)
AF:
AC:
0
AN:
4838
European-Finnish (FIN)
AF:
AC:
0
AN:
10630
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68040
Other (OTH)
AF:
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions as Germline
Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
Mucopolysaccharidosis, MPS-III-B (1)
-
1
-
Mucopolysaccharidosis, MPS-III-B;C5569050:Charcot-Marie-Tooth disease axonal type 2V (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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