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NM_000478.6(ALPL):c.1285G>A (p.Glu429Lys) AND not provided

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Nov 9, 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:
RCV003558529.2

Allele description [Variation Report for NM_000478.6(ALPL):c.1285G>A (p.Glu429Lys)]

NM_000478.6(ALPL):c.1285G>A (p.Glu429Lys)

Gene:
ALPL:alkaline phosphatase, biomineralization associated [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p36.12
Genomic location:
Preferred name:
NM_000478.6(ALPL):c.1285G>A (p.Glu429Lys)
HGVS:
  • NC_000001.11:g.21576617G>A
  • NG_008940.1:g.72253G>A
  • NM_000478.6:c.1285G>AMANE SELECT
  • NM_001127501.4:c.1120G>A
  • NM_001177520.3:c.1054G>A
  • NM_001369803.2:c.1285G>A
  • NM_001369804.2:c.1285G>A
  • NM_001369805.2:c.1285G>A
  • NP_000469.3:p.Glu429Lys
  • NP_001120973.2:p.Glu374Lys
  • NP_001170991.1:p.Glu352Lys
  • NP_001356732.1:p.Glu429Lys
  • NP_001356733.1:p.Glu429Lys
  • NP_001356734.1:p.Glu429Lys
  • NC_000001.10:g.21903110G>A
  • NM_000478.4:c.1285G>A
Protein change:
E352K
Links:
dbSNP: rs1553414868
NCBI 1000 Genomes Browser:
rs1553414868
Molecular consequence:
  • NM_000478.6:c.1285G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127501.4:c.1120G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001177520.3:c.1054G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369803.2:c.1285G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369804.2:c.1285G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369805.2:c.1285G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004291746Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Nov 9, 2022) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Mild forms of hypophosphatasia mostly result from dominant negative effect of severe alleles or from compound heterozygosity for severe and moderate alleles.

Fauvert D, Brun-Heath I, Lia-Baldini AS, Bellazi L, Taillandier A, Serre JL, de Mazancourt P, Mornet E.

BMC Med Genet. 2009 Jun 6;10:51. doi: 10.1186/1471-2350-10-51.

PubMed [citation]
PMID:
19500388
PMCID:
PMC2702372

Hypophosphatasia: validation and expansion of the clinical nosology for children from 25 years experience with 173 pediatric patients.

Whyte MP, Zhang F, Wenkert D, McAlister WH, Mack KE, Benigno MC, Coburn SP, Wagy S, Griffin DM, Ericson KL, Mumm S.

Bone. 2015 Jun;75:229-39. doi: 10.1016/j.bone.2015.02.022. Epub 2015 Feb 27.

PubMed [citation]
PMID:
25731960
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004291746.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects ALPL function (PMID: 19500388). 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 ALPL protein function. ClinVar contains an entry for this variant (Variation ID: 558387). This missense change has been observed in individual(s) with autosomal dominant hypophosphatasia (PMID: 19500388, 25731960). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 429 of the ALPL protein (p.Glu429Lys).

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

Last Updated: Sep 29, 2024