NM_000478.6(ALPL):c.581_582del (p.Pro194fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 1, 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:: RCV003738181.1

Allele description [Variation Report for NM_000478.6(ALPL):c.581_582del (p.Pro194fs)]

NM_000478.6(ALPL):c.581_582del (p.Pro194fs)

Gene:

ALPL:alkaline phosphatase, biomineralization associated [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1p36.12

Genomic location:

Preferred name:

NM_000478.6(ALPL):c.581_582del (p.Pro194fs)

HGVS:

NC_000001.11:g.21564149_21564150del
NG_008940.2:g.60167_60168del
NM_000478.6:c.581_582delMANE SELECT
NM_001127501.4:c.416_417del
NM_001177520.3:c.350_351del
NM_001369803.2:c.581_582del
NM_001369804.2:c.581_582del
NM_001369805.2:c.581_582del
NP_000469.3:p.Pro194fs
NP_001120973.2:p.Pro139fs
NP_001170991.1:p.Pro117fs
NP_001356732.1:p.Pro194fs
NP_001356733.1:p.Pro194fs
NP_001356734.1:p.Pro194fs
NC_000001.10:g.21890642_21890643del
NG_008940.1:g.59785_59786del

Protein change:

P117fs

Molecular consequence:

NM_000478.6:c.581_582del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127501.4:c.416_417del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001177520.3:c.350_351del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369803.2:c.581_582del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369804.2:c.581_582del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369805.2:c.581_582del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004554612	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 1, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 3174660, 10679946, 32973344, 33814268, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004554612

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 1, 2023)

germline

clinical testing

PubMed (5)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A missense mutation in the human liver/bone/kidney alkaline phosphatase gene causing a lethal form of hypophosphatasia.

Weiss MJ, Cole DE, Ray K, Whyte MP, Lafferty MA, Mulivor RA, Harris H.

Proc Natl Acad Sci U S A. 1988 Oct;85(20):7666-9.

PubMed [citation]

PMID:: 3174660
PMCID:: PMC282253

Fifteen new mutations (-195C>T, L-12X, 298-2A>G, T117N, A159T, R229S, 997+2T>A, E274X, A331T, H364R, D389G, 1256delC, R433H, N461I, C472S) in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in patients with hypophosphatasia.

Taillandier A, Cozien E, Muller F, Merrien Y, Bonnin E, Fribourg C, Simon-Bouy B, Serre JL, Bieth E, Brenner R, Cordier MP, De Bie S, Fellmann F, Freisinger P, Hesse V, Hennekam RC, Josifova D, Kerzin-Storrar L, Leporrier N, Zabot MT, Mornet E.

Hum Mutat. 2000 Mar;15(3):293.

PubMed [citation]

PMID:: 10679946

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV004554612.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1724538). This variant has not been reported in the literature in individuals affected with ALPL-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Pro194Argfs*8) in the ALPL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ALPL are known to be pathogenic (PMID: 3174660, 10679946, 32973344, 33814268).

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

Last Updated: Feb 28, 2024

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