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NM_000478.6(ALPL):c.346G>A (p.Ala116Thr) AND Childhood hypophosphatasia

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 1, 2003
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV000014668.20

Allele description [Variation Report for NM_000478.6(ALPL):c.346G>A (p.Ala116Thr)]

NM_000478.6(ALPL):c.346G>A (p.Ala116Thr)

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.346G>A (p.Ala116Thr)
Other names:
A99T
HGVS:
  • NC_000001.11:g.21563158G>A
  • NG_008940.1:g.58794G>A
  • NM_000478.6:c.346G>AMANE SELECT
  • NM_001127501.4:c.181G>A
  • NM_001177520.3:c.115G>A
  • NM_001369803.2:c.346G>A
  • NM_001369804.2:c.346G>A
  • NM_001369805.2:c.346G>A
  • NP_000469.3:p.Ala116Thr
  • NP_001120973.2:p.Ala61Thr
  • NP_001170991.1:p.Ala39Thr
  • NP_001356732.1:p.Ala116Thr
  • NP_001356733.1:p.Ala116Thr
  • NP_001356734.1:p.Ala116Thr
  • NC_000001.10:g.21889651G>A
  • NM_000478.4:c.346G>A
  • NM_000478.5:c.346G>A
  • P05186:p.Ala116Thr
Protein change:
A116T; ALA99THR
Links:
UniProtKB: P05186#VAR_013977; OMIM: 171760.0015; dbSNP: rs121918013
NCBI 1000 Genomes Browser:
rs121918013
Molecular consequence:
  • NM_000478.6:c.346G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127501.4:c.181G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001177520.3:c.115G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369803.2:c.346G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369804.2:c.346G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369805.2:c.346G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Childhood hypophosphatasia
Identifiers:
MedGen: C0220743; Orphanet: 436; OMIM: 241510

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000034923OMIM
no assertion criteria provided
Pathogenic
(Aug 1, 2003) 		germlineliterature only

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Characterization of a family with dominant hypophosphatasia.

Hu JC, Plaetke R, Mornet E, Zhang C, Sun X, Thomas HF, Simmer JP.

Eur J Oral Sci. 2000 Jun;108(3):189-94.

PubMed [citation]
PMID:
10872988

A molecular approach to dominance in hypophosphatasia.

Lia-Baldini AS, Muller F, Taillandier A, Gibrat JF, Mouchard M, Robin B, Simon-Bouy B, Serre JL, Aylsworth AS, Bieth E, Delanote S, Freisinger P, Hu JC, Krohn HP, Nunes ME, Mornet E.

Hum Genet. 2001 Jul;109(1):99-108.

PubMed [citation]
PMID:
11479741
See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000034923.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (3)

Description

In 13 affected members of a 4-generation Texas family segregating autosomal dominant hypophosphatasia in both children (241510) and adults (146300), Hu et al. (2000) identified heterozygosity for an ala99-to-thr (A99T) substitution in the ALPL gene. The mutation was also found in 1 clinically unaffected individual who had an elevated urinary phosphoethanolamine (PEA) level. Lia-Baldini et al. (2001) performed functional studies of the A99T mutation and observed a moderate dominant negative effect. Complete sequencing of the gene in the brother and sister twin probands from the Texas family, including the untranslated exon 1 and intron/exon borders, revealed no mutation other than the heterozygous 346G-A transition in exon 5 of the ALPL gene that results in the A99T substitution.

Herasse et al. (2003) identified the A99T mutation in heterozygous state in a 2-year-old male and his mother; the former had only dental manifestations and low serum alkaline phosphatase and the latter did not have odontohypophosphatasia (146300) but had an unusual number of dental caries and had had numerous treatments of dental root canals.

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

Last Updated: Mar 16, 2024