NM_000263.4(NAGLU):c.874G>A (p.Gly292Arg) AND Mucopolysaccharidosis, MPS-III-B

This record was updated by the submitter. Please see the current version.

Germline classification:: Conflicting interpretations of pathogenicity (4 submissions)
Last evaluated:: Feb 1, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV000668384.7

Allele description

NM_000263.4(NAGLU):c.874G>A (p.Gly292Arg)

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.874G>A (p.Gly292Arg)

Other names:

p.Gly292Arg

HGVS:

NC_000017.11:g.42541059G>A
NG_011552.1:g.10127G>A
NM_000263.4:c.874G>AMANE SELECT
NP_000254.2:p.Gly292Arg
NC_000017.10:g.40693077G>A
NM_000263.3:c.874G>A

Protein change:

G292R

Links:

dbSNP: rs1358994052

NCBI 1000 Genomes Browser:

rs1358994052

Molecular consequence:

NM_000263.4:c.874G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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

Recent activity

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wiskott-Aldrich syndrome protein family member 1 isoform X1 [Seriola dumerili]
wiskott-Aldrich syndrome protein family member 1 isoform X1 [Seriola dumerili]
gi|1250105255|ref|XP_022624657.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000792975	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Likely pathogenic (Jul 25, 2017)	unknown	clinical testing	PubMed (7) [See all records that cite these PMIDs] 10094189, 27590925, 9950362, 23380547, 22976768, 11153910, 14984474 Citation Link,
SCV000929907	Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 1, 2019)	germline	literature only	PubMed (4) [See all records that cite these PMIDs] 9950362, 23380547, 25741868, 30809705
SCV003926592	Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 25, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005051872	Laboratory of Medical Genetics, National & Kapodistrian University of Athens	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 1, 2024)	germline	curation	PubMed (1) [See all records that cite this PMID]

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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	no	not provided	not provided	not provided	not provided	not provided	curation
not provided	germline	yes	1	not provided	not provided	not provided	not provided	literature only, clinical testing

Citations

PubMed

Sanfilippo type B syndrome (mucopolysaccharidosis III B): allelic heterogeneity corresponds to the wide spectrum of clinical phenotypes.

Weber B, Guo XH, Kleijer WJ, van de Kamp JJ, Poorthuis BJ, Hopwood JJ.

Eur J Hum Genet. 1999 Jan;7(1):34-44.

PubMed [citation]

PMID:: 10094189

A prospective one-year natural history study of mucopolysaccharidosis types IIIA and IIIB: Implications for clinical trial design.

Truxal KV, Fu H, McCarty DM, McNally KA, Kunkler KL, Zumberge NA, Martin L, Aylward SC, Alfano LN, Berry KM, Lowes LP, Corridore M, McKee C, McBride KL, Flanigan KM.

Mol Genet Metab. 2016 Nov;119(3):239-248. doi: 10.1016/j.ymgme.2016.08.002. Epub 2016 Aug 18.

PubMed [citation]

PMID:: 27590925

See all PubMed Citations (9)

Details of each submission

From Counsyl, SCV000792975.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

#	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

From Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova, SCV000929907.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (4)

Description

PM2:Very low frequency in ExAC. PP3:multiple lines of computational evidence supporting a deleterious effect (DANN, MutationTaster, GERP, SIFT)

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

From Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics, SCV003926592.1

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

Description

A homozygous variation in exon 5 of the NAGLU gene that results in the amino acid substitution of arginine for glycine at codon 292 was detected. The observed variant c.874G>A (p.Gly292Arg) has not beeen reported in the 1000 genomes and has MAF of 0.0012% gnomAD databases. The in silico prediction of the variant is disease causing by PolyPhen-2, SIFT, MutationTaster and CADD. In summary, the variant meets our criteria to be classified as pathogenic.

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

From Laboratory of Medical Genetics, National & Kapodistrian University of Athens, SCV005051872.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 13, 2024

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