NM_000478.6(ALPL):c.542C>T (p.Ser181Leu) AND Infantile hypophosphatasia

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Feb 1, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000169128.6

Allele description [Variation Report for NM_000478.6(ALPL):c.542C>T (p.Ser181Leu)]

NM_000478.6(ALPL):c.542C>T (p.Ser181Leu)

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.542C>T (p.Ser181Leu)

HGVS:

NC_000001.11:g.21564110C>T
NG_008940.1:g.59746C>T
NM_000478.6:c.542C>TMANE SELECT
NM_001127501.4:c.377C>T
NM_001177520.3:c.311C>T
NM_001369803.2:c.542C>T
NM_001369804.2:c.542C>T
NM_001369805.2:c.542C>T
NP_000469.3:p.Ser181Leu
NP_001120973.2:p.Ser126Leu
NP_001170991.1:p.Ser104Leu
NP_001356732.1:p.Ser181Leu
NP_001356733.1:p.Ser181Leu
NP_001356734.1:p.Ser181Leu
NC_000001.10:g.21890603C>T
NM_000478.4:c.542C>T
NM_000478.5:c.542C>T
P05186:p.Ser181Leu

Protein change:

S104L

Links:

UniProtKB: P05186#VAR_013982; dbSNP: rs199590449

NCBI 1000 Genomes Browser:

rs199590449

Molecular consequence:

NM_000478.6:c.542C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001127501.4:c.377C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001177520.3:c.311C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001369803.2:c.542C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001369804.2:c.542C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001369805.2:c.542C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Infantile hypophosphatasia
Identifiers:: MedGen: C0268412; Orphanet: 436; OMIM: 241500

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000220338	Counsyl	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))	Likely pathogenic (May 21, 2014)	unknown	literature only	PubMed (4) [See all records that cite these PMIDs] 11479741, 21956185, 17253930, 16583935 Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015), Citation Link,
SCV002512239	Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 8, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005051910	Laboratory of Medical Genetics, National & Kapodistrian University of Athens	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 1, 2024)	germline	curation	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000220338

Counsyl

criteria provided, single submitter

(Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))

Likely pathogenic
(May 21, 2014)

unknown

literature only

PubMed (4)
[See all records that cite these PMIDs]

Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015),

Citation Link,

SCV002512239

Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 8, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV005051910

Laboratory of Medical Genetics, National & Kapodistrian University of Athens

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 1, 2024)

germline

curation

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

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

Rare coding variants in ALPL are associated with low serum alkaline phosphatase and low bone mineral density.

Nielson CM, Zmuda JM, Carlos AS, Wagoner WJ, Larson EA, Orwoll ES, Klein RF.

J Bone Miner Res. 2012 Jan;27(1):93-103. doi: 10.1002/jbmr.527.

PubMed [citation]

PMID:: 21956185
PMCID:: PMC3810303

See all PubMed Citations (5)

Details of each submission

From Counsyl, SCV000220338.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (4)

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

From Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein, SCV002512239.1

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

Description

ACMG classification criteria: PS3 supporting, PS4 moderate, PM2 moderate, PM3 strong, PP3 supporting

#	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		not provided	not provided	not provided	not provided

From Laboratory of Medical Genetics, National & Kapodistrian University of Athens, SCV005051910.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (1)

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

Last Updated: Sep 29, 2024

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