NM_000444.6(PHEX):c.750C>G (p.Tyr250Ter) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 30, 2020
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:: RCV001388467.8

Allele description [Variation Report for NM_000444.6(PHEX):c.750C>G (p.Tyr250Ter)]

NM_000444.6(PHEX):c.750C>G (p.Tyr250Ter)

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.750C>G (p.Tyr250Ter)

HGVS:

NC_000023.11:g.22094000C>G
NG_007563.2:g.66198C>G
NM_000444.6:c.750C>GMANE SELECT
NM_001282754.2:c.750C>G
NP_000435.3:p.Tyr250Ter
NP_001269683.1:p.Tyr250Ter
NC_000023.10:g.22112118C>G

Protein change:

Y250*

Links:

dbSNP: rs1322662992

NCBI 1000 Genomes Browser:

rs1322662992

Molecular consequence:

NM_000444.6:c.750C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001282754.2:c.750C>G - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Flavobacterium sp. IH3-5 16S ribosomal RNA gene, partial sequence
Flavobacterium sp. IH3-5 16S ribosomal RNA gene, partial sequence
gi|55831331|gb|AY789577.1|

Nucleotide
uncharacterized protein Dmel_CG5056 [Drosophila melanogaster]
uncharacterized protein Dmel_CG5056 [Drosophila melanogaster]
gi|24583382|ref|NP_609391.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001589466	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 30, 2020)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 9097956, 9106524, 19219621, 21902834, 9768674, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001589466

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 30, 2020)

germline

clinical testing

PubMed (6)
[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

Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP).

Rowe PS, Oudet CL, Francis F, Sinding C, Pannetier S, Econs MJ, Strom TM, Meitinger T, Garabedian M, David A, Macher MA, Questiaux E, Popowska E, Pronicka E, Read AP, Mokrzycki A, Glorieux FH, Drezner MK, Hanauer A, Lehrach H, Goulding JN, O'Riordan JL.

Hum Mol Genet. 1997 Apr;6(4):539-49.

PubMed [citation]

PMID:: 9097956

Mutational analysis of the PEX gene in patients with X-linked hypophosphatemic rickets.

Holm IA, Huang X, Kunkel LM.

Am J Hum Genet. 1997 Apr;60(4):790-7.

PubMed [citation]

PMID:: 9106524
PMCID:: PMC1712471

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001589466.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in PHEX are known to be pathogenic (PMID: 9097956, 9106524, 19219621). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This nonsense change has been observed in individual(s) with hypophosphatemic rickets (PMID: 21902834, 9768674). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Tyr250*) in the PHEX gene. It is expected to result in an absent or disrupted protein product.

#	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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