NM_000478.6(ALPL):c.286G>C (p.Ala96Pro) AND Hypophosphatasia

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Apr 25, 2023
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:: RCV003448898.1

Allele description [Variation Report for NM_000478.6(ALPL):c.286G>C (p.Ala96Pro)]

NM_000478.6(ALPL):c.286G>C (p.Ala96Pro)

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.286G>C (p.Ala96Pro)

HGVS:

NC_000001.11:g.21561201G>C
NG_008940.1:g.56837G>C
NG_008940.2:g.57219G>C
NM_000478.6:c.286G>CMANE SELECT
NM_001127501.4:c.121G>C
NM_001177520.3:c.66+456G>C
NM_001369803.2:c.286G>C
NM_001369804.2:c.286G>C
NM_001369805.2:c.286G>C
NP_000469.3:p.Ala96Pro
NP_001120973.2:p.Ala41Pro
NP_001356732.1:p.Ala96Pro
NP_001356733.1:p.Ala96Pro
NP_001356734.1:p.Ala96Pro
NC_000001.10:g.21887694G>C

Protein change:

A41P

Molecular consequence:

NM_001177520.3:c.66+456G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000478.6:c.286G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127501.4:c.121G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001369803.2:c.286G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001369804.2:c.286G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001369805.2:c.286G>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Hypophosphatasia
Synonyms:: Phosphoethanol-aminuria
Identifiers:: MONDO: MONDO:0018570; MedGen: C0020630

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004175712	JKU Lab, Dept of Paediatrics, Johannes Kepler University	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 25, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 33191482, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004175712

JKU Lab, Dept of Paediatrics, Johannes Kepler University

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Apr 25, 2023)

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
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genotype-Phenotype Associations in 72 Adults with Suspected ALPL-Associated Hypophosphatasia.

Jandl NM, Schmidt T, Rolvien T, Stürznickel J, Chrysostomou K, von Vopelius E, Volk AE, Schinke T, Kubisch C, Amling M, Barvencik F.

Calcif Tissue Int. 2021 Mar;108(3):288-301. doi: 10.1007/s00223-020-00771-7. Epub 2020 Nov 15.

PubMed [citation]

PMID:: 33191482
PMCID:: PMC7881968

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 JKU Lab, Dept of Paediatrics, Johannes Kepler University, SCV004175712.1

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

Description

Absent in GnomAD. Functional testing at the JKU lab showed reduced ALP residual activity. The functional test results and ACMG criteria applied can be looked up in the ALPL gene variant database. https://alplmutationdatabase.jku.at/

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Dec 17, 2023

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