U.S. flag

An official website of the United States government

NM_000478.6(ALPL):c.571G>A (p.Glu191Lys) AND Inborn genetic diseases

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 2, 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:
RCV002513051.8

Allele description

NM_000478.6(ALPL):c.571G>A (p.Glu191Lys)

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.571G>A (p.Glu191Lys)
Other names:
E174K
HGVS:
  • NC_000001.11:g.21564139G>A
  • NG_008940.1:g.59775G>A
  • NM_000478.6:c.571G>AMANE SELECT
  • NM_001127501.4:c.406G>A
  • NM_001177520.3:c.340G>A
  • NM_001369803.2:c.571G>A
  • NM_001369804.2:c.571G>A
  • NM_001369805.2:c.571G>A
  • NP_000469.3:p.Glu191Lys
  • NP_000469.3:p.Glu191Lys
  • NP_001120973.2:p.Glu136Lys
  • NP_001170991.1:p.Glu114Lys
  • NP_001356732.1:p.Glu191Lys
  • NP_001356733.1:p.Glu191Lys
  • NP_001356734.1:p.Glu191Lys
  • NC_000001.10:g.21890632G>A
  • NM_000478.3:c.571G>A
  • NM_000478.4:c.571G>A
  • NM_000478.5:c.571G>A
  • P05186:p.Glu191Lys
Protein change:
E114K; GLU174LYS
Links:
UniProtKB: P05186#VAR_006158; OMIM: 171760.0008; dbSNP: rs121918007
NCBI 1000 Genomes Browser:
rs121918007
Molecular consequence:
  • NM_000478.6:c.571G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127501.4:c.406G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001177520.3:c.340G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369803.2:c.571G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369804.2:c.571G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369805.2:c.571G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Inborn genetic diseases
Identifiers:
MeSH: D030342; MedGen: C0950123

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003730807Ambry Genetics
criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)		Pathogenic
(Aug 2, 2022) 		germlineclinical testing

PubMed (9)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Evidence of a founder effect for the tissue-nonspecific alkaline phosphatase (TNSALP) gene E174K mutation in hypophosphatasia patients.

Hérasse M, Spentchian M, Taillandier A, Mornet E.

Eur J Hum Genet. 2002 Oct;10(10):666-8.

PubMed [citation]
PMID:
12357339

Hypophosphatasia: a genetic-based nosology and new insights in genotype-phenotype correlation.

Mornet E, Taillandier A, Domingues C, Dufour A, Benaloun E, Lavaud N, Wallon F, Rousseau N, Charle C, Guberto M, Muti C, Simon-Bouy B.

Eur J Hum Genet. 2021 Feb;29(2):289-299. doi: 10.1038/s41431-020-00732-6. Epub 2020 Sep 24.

PubMed [citation]
PMID:
32973344
PMCID:
PMC7868366
See all PubMed Citations (9)

Details of each submission

From Ambry Genetics, SCV003730807.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (9)

Description

The c.571G>A (p.E191K) alteration is located in exon 6 (coding exon 5) of the ALPL gene. This alteration results from a G to A substitution at nucleotide position 571, causing the glutamic acid (E) at amino acid position 191 to be replaced by a lysine (K). Based on data from gnomAD, the A allele has an overall frequency of 0.25% (699/282574) total alleles studied. The highest observed frequency was 1.65% (414/25032) of European (Finnish) alleles. This variant, also described as E174K in literature, is a common founder mutation accounting for up to approximately 10% of disease-causing mutations in the ALPL gene (Hérasse, 2002; Mornet, 2021). This variant has been reported in the heterozygous (Hofmann, 2014; Taillandier, 2018; Mornet, 2021; Ambry internal data) and compound heterozygous (Henthorn, 1992; Schalin-Jäntti, 2010; Hofmann, 2014; Zurutuza, 1999; Mornet, 2021; Sperelakis-Beedham, 2021) states in individuals with hypophosphatasia and low alkaline phosphatase, with the clinical severity correlating with degree of loss of function. This amino acid position is not well conserved in available vertebrate species. Multiple in vitro functional studies using transient expression in cells show slightly reduced activity consistent with a mild loss of function allele based on comparison to wild type and pathogenic controls (Hofmann, 2014; Zurutuza, 1999; Del Angel, 2020). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Apr 20, 2024