NM_000444.6(PHEX):c.2100del (p.Ala701fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 7, 2021
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:: RCV001206110.4

Allele description [Variation Report for NM_000444.6(PHEX):c.2100del (p.Ala701fs)]

NM_000444.6(PHEX):c.2100del (p.Ala701fs)

Genes:

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

Variant type:

Deletion

Cytogenetic location:

Xp22.11

Genomic location:

Preferred name:

NM_000444.6(PHEX):c.2100del (p.Ala701fs)

HGVS:

NC_000023.11:g.22245362del
NG_007563.2:g.217559del
NM_000444.6:c.2100delMANE SELECT
NM_001282754.2:c.2071-2489del
NP_000435.3:p.Ala701fs
NC_000023.10:g.22263479del
NM_000444.5:c.2100del

Protein change:

A701fs

Links:

dbSNP: rs1936360966

NCBI 1000 Genomes Browser:

rs1936360966

Molecular consequence:

NM_000444.6:c.2100del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001282754.2:c.2071-2489del - intron variant - [Sequence Ontology: SO:0001627]

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
SCV001377401	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 7, 2021)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 9097956, 9768674, 21902834, 23079138, 29505567, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001377401

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 7, 2021)

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 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 (6)

Details of each submission

From Invitae, SCV001377401.5

#	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. This variant disrupts a region of the PHEX protein in which other variant(s) (p.Arg702*) have been determined to be pathogenic (PMID: 9097956, 9768674, 21902834, 23079138, 29505567). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 937153). This premature translational stop signal has been observed in individual(s) with X-linked hypophosphatemia (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala701Profs*39) in the PHEX gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 49 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: Feb 20, 2024

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