NM_000263.4(NAGLU):c.1348C>T (p.Gln450Ter) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 23, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003794451.1

Allele description [Variation Report for NM_000263.4(NAGLU):c.1348C>T (p.Gln450Ter)]

NM_000263.4(NAGLU):c.1348C>T (p.Gln450Ter)

Gene:

NAGLU:N-acetyl-alpha-glucosaminidase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q21.2

Genomic location:

Preferred name:

NM_000263.4(NAGLU):c.1348C>T (p.Gln450Ter)

HGVS:

NC_000017.11:g.42543354C>T
NG_011552.1:g.12422C>T
NM_000263.4:c.1348C>TMANE SELECT
NP_000254.2:p.Gln450Ter
NC_000017.10:g.40695372C>T

Protein change:

Q450*

Molecular consequence:

NM_000263.4:c.1348C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Mucopolysaccharidosis, MPS-III-B (MPS3B)
Synonyms:: NAGLU DEFICIENCY; Mucopoly-saccharidosis type 3B; Sanfilippo syndrome B; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009656; MedGen: C0086648; OMIM: 252920

Name:: Charcot-Marie-Tooth disease axonal type 2V
Synonyms:: CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 2V; CHARCOT-MARIE-TOOTH DISEASE, AXONAL, AUTOSOMAL DOMINANT, TYPE 2V
Identifiers:: MONDO: MONDO:0014665; MedGen: C5569050; Orphanet: 447964; OMIM: 616491

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004585251	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 23, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 9443875, 29979746, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004585251

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 23, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genotype-phenotype correspondence in Sanfilippo syndrome type B.

Zhao HG, Aronovich EL, Whitley CB.

Am J Hum Genet. 1998 Jan;62(1):53-63.

PubMed [citation]

PMID:: 9443875
PMCID:: PMC1376807

Utilizing ExAC to assess the hidden contribution of variants of unknown significance to Sanfilippo Type B incidence.

Clark WT, Yu GK, Aoyagi-Scharber M, LeBowitz JH.

PLoS One. 2018;13(7):e0200008. doi: 10.1371/journal.pone.0200008.

PubMed [citation]

PMID:: 29979746
PMCID:: PMC6034809

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV004585251.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the NAGLU protein in which other variant(s) (p.Tyr455Cys) have been determined to be pathogenic (PMID: 9443875, 29979746). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with NAGLU-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Gln450*) in the NAGLU gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 294 amino acid(s) of the NAGLU protein.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 5, 2024

ClinVar

Relating variation to medicine