NM_000444.6(PHEX):c.755T>C (p.Phe252Ser) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 29, 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:: RCV001857790.14

Allele description [Variation Report for NM_000444.6(PHEX):c.755T>C (p.Phe252Ser)]

NM_000444.6(PHEX):c.755T>C (p.Phe252Ser)

Gene:

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.755T>C (p.Phe252Ser)

Other names:

F249S

HGVS:

NC_000023.11:g.22094005T>C
NG_007563.2:g.66203T>C
NM_000444.6:c.755T>CMANE SELECT
NM_001282754.2:c.755T>C
NP_000435.3:p.Phe252Ser
NP_001269683.1:p.Phe252Ser
NC_000023.10:g.22112123T>C
NG_007563.1:g.66203T>C
NM_000444.4:c.755T>C
P78562:p.Phe252Ser

Protein change:

F252S; PHE249SER

Links:

UniProtKB: P78562#VAR_006742; OMIM: 300550.0006; dbSNP: rs267606945

NCBI 1000 Genomes Browser:

rs267606945

Molecular consequence:

NM_000444.6:c.755T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001282754.2:c.755T>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002230655	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 29, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 11502829, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002230655

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 29, 2022)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutational analysis and genotype-phenotype correlation of the PHEX gene in X-linked hypophosphatemic rickets.

Holm IA, Nelson AE, Robinson BG, Mason RS, Marsh DJ, Cowell CT, Carpenter TO.

J Clin Endocrinol Metab. 2001 Aug;86(8):3889-99.

PubMed [citation]

PMID:: 11502829

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002230655.3

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

Description

This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PHEX protein function. This missense change has been observed in individuals with X-linked hypophosphatemic rickets (PMID: 11502829; Invitae). It has also been observed to segregate with disease in related individuals. This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 252 of the PHEX protein (p.Phe252Ser).

#	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: Oct 26, 2024

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