NM_000444.6(PHEX):c.2182C>T (p.Gln728Ter) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 22, 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:: RCV001390160.7

Allele description [Variation Report for NM_000444.6(PHEX):c.2182C>T (p.Gln728Ter)]

NM_000444.6(PHEX):c.2182C>T (p.Gln728Ter)

Genes:

PTCHD1-AS:PTCHD1 antisense RNA (head to head) [Gene - HGNC]
PHEX:phosphate regulating endopeptidase X-linked [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp22.11

Genomic location:

Preferred name:

NM_000444.6(PHEX):c.2182C>T (p.Gln728Ter)

HGVS:

NC_000023.11:g.22247885C>T
NG_007563.2:g.220082C>T
NM_000444.6:c.2182C>TMANE SELECT
NM_001282754.2:c.*17C>T
NP_000435.3:p.Gln728Ter
NC_000023.10:g.22266002C>T

Protein change:

Q728*

Links:

dbSNP: rs2147217296

NCBI 1000 Genomes Browser:

rs2147217296

Molecular consequence:

NM_001282754.2:c.*17C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000444.6:c.2182C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV001591797	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 22, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 9199930, 9768674, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001591797

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 22, 2022)

germline

clinical testing

PubMed (3)
[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

Genomic organization of the human PEX gene mutated in X-linked dominant hypophosphatemic rickets.

Francis F, Strom TM, Hennig S, Böddrich A, Lorenz B, Brandau O, Mohnike KL, Cagnoli M, Steffens C, Klages S, Borzym K, Pohl T, Oudet C, Econs MJ, Rowe PS, Reinhardt R, Meitinger T, Lehrach H.

Genome Res. 1997 Jun;7(6):573-85. No abstract available.

PubMed [citation]

PMID:: 9199930

Mutational analysis of PHEX gene in X-linked hypophosphatemia.

Dixon PH, Christie PT, Wooding C, Trump D, Grieff M, Holm I, Gertner JM, Schmidtke J, Shah B, Shaw N, Smith C, Tau C, Schlessinger D, Whyte MP, Thakker RV.

J Clin Endocrinol Metab. 1998 Oct;83(10):3615-23.

PubMed [citation]

PMID:: 9768674

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001591797.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the PHEX protein in which other variant(s) (p.Arg747*) have been determined to be pathogenic (PMID: 9199930, 9768674). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1076296). This premature translational stop signal has been observed in individual(s) with hypophosphatemia (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln728*) in the PHEX gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 22 amino acid(s) of the PHEX protein.

#	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: Sep 29, 2024

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