U.S. flag

An official website of the United States government

NM_000444.6(PHEX):c.770C>A (p.Ala257Asp) AND not provided

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Mar 13, 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:
RCV002627578.3

Allele description [Variation Report for NM_000444.6(PHEX):c.770C>A (p.Ala257Asp)]

NM_000444.6(PHEX):c.770C>A (p.Ala257Asp)

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.770C>A (p.Ala257Asp)
HGVS:
  • NC_000023.11:g.22094020C>A
  • NG_007563.2:g.66218C>A
  • NG_007563.3:g.66697C>A
  • NM_000444.6:c.770C>AMANE SELECT
  • NM_001282754.2:c.770C>A
  • NP_000435.3:p.Ala257Asp
  • NP_001269683.1:p.Ala257Asp
  • NC_000023.10:g.22112138C>A
Protein change:
A257D
Molecular consequence:
  • NM_000444.6:c.770C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001282754.2:c.770C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002979034Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Mar 13, 2022) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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, SCV002979034.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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 individual(s) with clinical features of hypophosphatemic rickets (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 257 of the PHEX protein (p.Ala257Asp).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024