NM_000262.3(NAGA):c.487G>A (p.Glu163Lys) AND Alpha-N-acetylgalactosaminidase deficiency type 1

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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 18, 2022
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:: RCV000817487.5

Allele description

NM_000262.3(NAGA):c.487G>A (p.Glu163Lys)

Genes:

LOC126863160:CDK7 strongly-dependent group 2 enhancer GRCh37_chr22:42462918-42464117 [Gene]
NAGA:alpha-N-acetylgalactosaminidase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q13.2

Genomic location:

Preferred name:

NM_000262.3(NAGA):c.487G>A (p.Glu163Lys)

HGVS:

NC_000022.11:g.42067128C>T
NG_009247.1:g.8715G>A
NM_000262.3:c.487G>AMANE SELECT
NM_001362848.1:c.487G>A
NM_001362850.1:c.487G>A
NP_000253.1:p.Glu163Lys
NP_001349777.1:p.Glu163Lys
NP_001349779.1:p.Glu163Lys
NC_000022.10:g.42463132C>T
NM_000262.2:c.487G>A

Protein change:

E163K

Links:

dbSNP: rs372458856

NCBI 1000 Genomes Browser:

rs372458856

Molecular consequence:

NM_000262.3:c.487G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001362848.1:c.487G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001362850.1:c.487G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Alpha-N-acetylgalactosaminidase deficiency type 1
Synonyms:: SCHINDLER DISEASE, TYPE I; ALPHA-N-ACETYLGALACTOSAMINIDASE DEFICIENCY, TYPE I; NAGA DEFICIENCY, TYPE I; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012221; MedGen: C1836544; Orphanet: 3137; Orphanet: 79279; Orphanet: 79281; OMIM: 609241

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000958051	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 18, 2022)	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

SCV000958051

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 18, 2022)

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 Invitae, SCV000958051.3

#	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 glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 163 of the NAGA protein (p.Glu163Lys). This variant is present in population databases (rs372458856, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with NAGA-related conditions. ClinVar contains an entry for this variant (Variation ID: 660319). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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: Jun 17, 2024

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