rs1057518896
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000444.6(PHEX):c.2167_2170dup(p.Phe724Ter) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 23)
Consequence
PHEX
NM_000444.6 frameshift
NM_000444.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.30
Genes affected
PHEX (HGNC:8918): (phosphate regulating endopeptidase X-linked) The protein encoded by this gene is a transmembrane endopeptidase that belongs to the type II integral membrane zinc-dependent endopeptidase family. The protein is thought to be involved in bone and dentin mineralization and renal phosphate reabsorption. Mutations in this gene cause X-linked hypophosphatemic rickets. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 30 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-22247868-G-GTAAC is Pathogenic according to our data. Variant chrX-22247868-G-GTAAC is described in ClinVar as [Pathogenic]. Clinvar id is 374096.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHEX | NM_000444.6 | c.2167_2170dup | p.Phe724Ter | frameshift_variant | 22/22 | ENST00000379374.5 | |
PTCHD1-AS | NR_073010.2 | n.850+6070_850+6071insGTTA | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHEX | ENST00000379374.5 | c.2167_2170dup | p.Phe724Ter | frameshift_variant | 22/22 | 1 | NM_000444.6 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
GnomAD4 exome Cov.: 28
GnomAD4 exome
Cov.:
28
GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Lower limb pain;C1704375:Hypophosphatemic rickets;C5574706:Bowing of the legs Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Aug 18, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at