NM_000478.6(ALPL):c.1479C>A (p.Asn493Lys) AND Childhood hypophosphatasia

Germline classification:: Pathogenic (1 submission)
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:: RCV001789735.2

Allele description [Variation Report for NM_000478.6(ALPL):c.1479C>A (p.Asn493Lys)]

NM_000478.6(ALPL):c.1479C>A (p.Asn493Lys)

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.1479C>A (p.Asn493Lys)

HGVS:

NC_000001.11:g.21577552C>A
NG_008940.1:g.73188C>A
NM_000478.6:c.1479C>AMANE SELECT
NM_001127501.4:c.1314C>A
NM_001177520.3:c.1248C>A
NM_001369803.2:c.1479C>A
NM_001369804.2:c.1479C>A
NM_001369805.2:c.1479C>A
NP_000469.3:p.Asn493Lys
NP_001120973.2:p.Asn438Lys
NP_001170991.1:p.Asn416Lys
NP_001356732.1:p.Asn493Lys
NP_001356733.1:p.Asn493Lys
NP_001356734.1:p.Asn493Lys
NC_000001.10:g.21904045C>A

Protein change:

N416K

Links:

dbSNP: rs759758484

NCBI 1000 Genomes Browser:

rs759758484

Molecular consequence:

NM_000478.6:c.1479C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127501.4:c.1314C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001177520.3:c.1248C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369803.2:c.1479C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369804.2:c.1479C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369805.2:c.1479C>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002032066	Center of Excellence in Genomics and Precision Dentistry, Faculty of Dentistry, Chulalongkorn University	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	paternal, germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28763161, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002032066

Center of Excellence in Genomics and Precision Dentistry, Faculty of Dentistry, Chulalongkorn University

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

paternal, germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
Thai	germline	no	1	not provided	not provided	not provided	not provided	clinical testing
Thai	paternal	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Monoallelic FGFR3 and Biallelic ALPL mutations in a Thai girl with hypochondroplasia and hypophosphatasia.

Porntaveetus T, Srichomthong C, Suphapeetiporn K, Shotelersuk V.

Am J Med Genet A. 2017 Oct;173(10):2747-2752. doi: 10.1002/ajmg.a.38370. Epub 2017 Aug 1.

PubMed [citation]

PMID:: 28763161

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Center of Excellence in Genomics and Precision Dentistry, Faculty of Dentistry, Chulalongkorn University, SCV002032066.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Thai	1	not provided	not provided	clinical testing	PubMed (2)
2	Thai	1	not provided	not provided	clinical testing	PubMed (2)

Description

Compound heterozygous with c.1460C>T (p.Ala487Val) in ALPL gene

Unaffected father

Description

The compound heterozygous variants, c.1460C>T (p.Ala487Val) and c.1479C>A (p.Asn493Lys), in ALPL gene were identified in a patient diagnosed with hypochondroplasia (HCH) and hypophosphatasia (HPP). Her mother was heterozygous for the c.1460C>T (p.Ala487Val) while her father was heterozygous for the c.1479C>A (p.Asn493Lys). Both altered amino acid positions are highly conserved among species. She was also identified the with the heterozygous missense variant, c.1612A>G (p.Ile538Val) in FGFR3 (Porntaveetus et al., 2017).

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

Last Updated: Mar 30, 2024

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