NM_000263.4(NAGLU):c.419A>G (p.Tyr140Cys) AND multiple conditions

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 18, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000705481.9

Allele description [Variation Report for NM_000263.4(NAGLU):c.419A>G (p.Tyr140Cys)]

NM_000263.4(NAGLU):c.419A>G (p.Tyr140Cys)

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.419A>G (p.Tyr140Cys)

HGVS:

NC_000017.11:g.42537433A>G
NG_011552.1:g.6501A>G
NM_000263.4:c.419A>GMANE SELECT
NP_000254.2:p.Tyr140Cys
NC_000017.10:g.40689451A>G
NM_000263.3:c.419A>G

Protein change:

Y140C

Links:

dbSNP: rs753520553

NCBI 1000 Genomes Browser:

rs753520553

Molecular consequence:

NM_000263.4:c.419A>G - missense variant - [Sequence Ontology: SO:0001583]

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

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probable LRR receptor-like serine/threonine-protein kinase At5g10290 isoform X2 ...
probable LRR receptor-like serine/threonine-protein kinase At5g10290 isoform X2 [Cucumis melo]
gi|659107713|ref|XP_008453818.1|

Protein
uncharacterized protein LOC111008257 isoform X3 [Momordica charantia]
uncharacterized protein LOC111008257 isoform X3 [Momordica charantia]
gi|1229767576|ref|XP_022136589.1|

Protein
uncharacterized protein LOC111008257 isoform X2 [Momordica charantia]
uncharacterized protein LOC111008257 isoform X2 [Momordica charantia]
gi|1229767574|ref|XP_022136588.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000834480	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 18, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 9443875, 9443878, 9950362, 11153910, 26907177, 28492532
SCV002809366	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 26, 2022)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000834480

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 18, 2024)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

SCV002809366

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 26, 2022)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

NAGLU mutations underlying Sanfilippo syndrome type B.

Schmidtchen A, Greenberg D, Zhao HG, Li HH, Huang Y, Tieu P, Zhao HZ, Cheng S, Zhao Z, Whitley CB, Di Natale P, Neufeld EF.

Am J Hum Genet. 1998 Jan;62(1):64-9.

PubMed [citation]

PMID:: 9443878
PMCID:: PMC1376809

See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000834480.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 140 of the NAGLU protein (p.Tyr140Cys). This variant is present in population databases (rs753520553, gnomAD 0.006%). This missense change has been observed in individuals with autosomal recessive mucopolysaccharidosis IIIB (PMID: 9443875, 9443878, 9950362, 11153910, 26907177). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 371634). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NAGLU protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.

#	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

From Fulgent Genetics, Fulgent Genetics, SCV002809366.1

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

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

Last Updated: Oct 20, 2024

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