rs796052123
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000263.4(NAGLU):c.367G>T(p.Glu123Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
NAGLU
NM_000263.4 stop_gained
NM_000263.4 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 3.61
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 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 17-42536639-G-T is Pathogenic according to our data. Variant chr17-42536639-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 204586.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NAGLU | NM_000263.4 | c.367G>T | p.Glu123Ter | stop_gained | 1/6 | ENST00000225927.7 | |
NAGLU | XM_024450771.2 | c.367G>T | p.Glu123Ter | stop_gained | 1/7 | ||
NAGLU | XM_047436138.1 | c.-95G>T | 5_prime_UTR_variant | 1/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NAGLU | ENST00000225927.7 | c.367G>T | p.Glu123Ter | stop_gained | 1/6 | 1 | NM_000263.4 | P1 | |
NAGLU | ENST00000586516.5 | c.119G>T | p.Arg40Leu | missense_variant | 1/4 | 2 | |||
NAGLU | ENST00000591587.1 | c.110G>T | p.Arg37Leu | missense_variant | 1/4 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1347364Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 664082
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1347364
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
664082
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Mucopolysaccharidosis, MPS-III-B;C5569050:Charcot-Marie-Tooth disease axonal type 2V Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 30, 2020 | This variant has been observed in individual(s) with late-onset painful sensory polyneuropathy (PMID: 25818867). ClinVar contains an entry for this variant (Variation ID: 204586). For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in NAGLU are known to be pathogenic (PMID: 9832037, 10094189, 16151907). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change creates a premature translational stop signal (p.Glu123*) in the NAGLU gene. It is expected to result in an absent or disrupted protein product. - |
not provided Uncertain:1
Uncertain significance, no assertion criteria provided | literature only | OMIM | Jun 01, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A
Vest4
GERP RS
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