NM_000263.4(NAGLU):c.2068A>T (p.Ile690Phe) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 21, 2021
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:: RCV001996513.3

Allele description [Variation Report for NM_000263.4(NAGLU):c.2068A>T (p.Ile690Phe)]

NM_000263.4(NAGLU):c.2068A>T (p.Ile690Phe)

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.2068A>T (p.Ile690Phe)

HGVS:

NC_000017.11:g.42544074A>T
NG_011552.1:g.13142A>T
NM_000263.4:c.2068A>TMANE SELECT
NP_000254.2:p.Ile690Phe
NC_000017.10:g.40696092A>T

Protein change:

I690F

Links:

dbSNP: rs143906118

NCBI 1000 Genomes Browser:

rs143906118

Molecular consequence:

NM_000263.4:c.2068A>T - 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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unnamed protein product [Aspergillus niger]
unnamed protein product [Aspergillus niger]
gi|134075671|emb|CAK96563.1|

Protein
cell wall organization and biogenesis-related protein, putative [Cryptococcus ne...
cell wall organization and biogenesis-related protein, putative [Cryptococcus neoformans var. neoformans JEC21]
gi|57223035|gb|AAW41079.1||gnl|tigr CNA05790.1

Protein
NADH dehydrogenase subunit 6 (mitochondrion) [Gonodactylaceus sp.]
NADH dehydrogenase subunit 6 (mitochondrion) [Gonodactylaceus sp.]
gi|2806885840|gb|XHB32438.1|

Protein
AGENCOURT_14149664 NICHD_XGC_Brn1 Xenopus laevis cDNA clone IMAGE:6949834 5', mR...
AGENCOURT_14149664 NICHD_XGC_Brn1 Xenopus laevis cDNA clone IMAGE:6949834 5', mRNA sequence
gi|31093088|gnl|dbEST|18297418|gb|C 57.1|

Nucleotide
Eukaryotic Initiation Factor-5
Eukaryotic Initiation Factor-5
A eukaryotic initiation factor that interacts with the 40S initiation complex and promotes the hydrolysis of the bound GTP. The hydrolysis of GTP causes the release of EUKARYO...<br/>Year introduced: 2003

MeSH

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002287073	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 21, 2021)	germline	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

SCV002287073

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 21, 2021)

germline

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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002287073.2

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

Description

This sequence change replaces isoleucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 690 of the NAGLU protein (p.Ile690Phe). This variant is present in population databases (no rsID available, gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NAGLU-related conditions. 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 not expected to disrupt NAGLU protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Sep 29, 2024

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