rs1556138590
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000444.6(PHEX):c.1832_1833del(p.Phe611Ter) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 23)
Consequence
PHEX
NM_000444.6 frameshift
NM_000444.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.22
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 undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-22221674-GTT-G is Pathogenic according to our data. Variant chrX-22221674-GTT-G is described in ClinVar as [Pathogenic]. Clinvar id is 438571.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-22221674-GTT-G is described in Lovd as [Pathogenic]. Variant chrX-22221674-GTT-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHEX | NM_000444.6 | c.1832_1833del | p.Phe611Ter | frameshift_variant | 18/22 | ENST00000379374.5 | |
PTCHD1-AS | NR_073010.2 | n.1048+5794_1048+5795del | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHEX | ENST00000379374.5 | c.1832_1833del | p.Phe611Ter | frameshift_variant | 18/22 | 1 | NM_000444.6 | P1 | |
PTCHD1-AS | ENST00000669979.1 | n.325+5794_325+5795del | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
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
Familial X-linked hypophosphatemic vitamin D refractory rickets Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München | Aug 31, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: -1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at