NM_000262.3(NAGA):c.406G>A (p.Asp136Asn) AND not specified

Clinical significance:Uncertain significance (Last evaluated: May 11, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001199905.1

Allele description [Variation Report for NM_000262.3(NAGA):c.406G>A (p.Asp136Asn)]

NM_000262.3(NAGA):c.406G>A (p.Asp136Asn)

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.406G>A (p.Asp136Asn)
HGVS:
  • NC_000022.11:g.42067209C>T
  • NG_009247.1:g.8634G>A
  • NM_000262.3:c.406G>AMANE SELECT
  • NM_001362848.1:c.406G>A
  • NM_001362850.1:c.406G>A
  • NP_000253.1:p.Asp136Asn
  • NP_001349777.1:p.Asp136Asn
  • NP_001349779.1:p.Asp136Asn
  • NC_000022.10:g.42463213C>T
  • NM_000262.2:c.406G>A
Protein change:
D136N
Links:
dbSNP: rs186173534
NCBI 1000 Genomes Browser:
rs186173534
Molecular consequence:
  • NM_000262.3:c.406G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001362848.1:c.406G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001362850.1:c.406G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001370664Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Uncertain significance
(May 11, 2020)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001370664.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Variant summary: NAGA c.406G>A (p.Asp136Asn) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0007 in 282862 control chromosomes, predominantly at a frequency of 0.014 within the Ashkenazi Jewish subpopulation in the gnomAD database, including 1 homozygote. Since the clinical phenotype associated with alpha-N-acetylgalactosaminidase deficiency varies vastly, from asymptomatic to severe infantile form of the disease, even in individuals with the same genotype (see e.g. PMID: 31468281), this relatively high frequency and a single homozygous occurrence in controls might not exclude the association of this variant with disease. To our knowledge, no occurrence of c.406G>A in individuals affected with Kanzaki Disease and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as benign, and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, until further evidence becomes available, the variant was classified as uncertain significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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