rs748792378
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Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS2_Supporting
The NM_000444.6(PHEX):c.1952G>A(p.Arg651Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000791 in 1,200,938 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 40 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000055 ( 0 hom., 2 hem., cov: 21)
Exomes 𝑓: 0.000082 ( 0 hom. 38 hem. )
Consequence
PHEX
NM_000444.6 missense
NM_000444.6 missense
Scores
6
8
3
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 8.04
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 Likely_benign. Variant got -1 ACMG points.
BS2
High Hemizygotes in GnomAd4 at 2 XL geneVariant has number of hemizygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PHEX | NM_000444.6 | c.1952G>A | p.Arg651Gln | missense_variant | 19/22 | ENST00000379374.5 | NP_000435.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PHEX | ENST00000379374.5 | c.1952G>A | p.Arg651Gln | missense_variant | 19/22 | 1 | NM_000444.6 | ENSP00000368682.4 |
Frequencies
GnomAD3 genomes AF: 0.0000550 AC: 6AN: 109054Hom.: 0 Cov.: 21 AF XY: 0.0000637 AC XY: 2AN XY: 31390
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GnomAD3 exomes AF: 0.0000382 AC: 7AN: 183443Hom.: 0 AF XY: 0.0000589 AC XY: 4AN XY: 67895
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GnomAD4 exome AF: 0.0000815 AC: 89AN: 1091884Hom.: 0 Cov.: 29 AF XY: 0.000106 AC XY: 38AN XY: 357496
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GnomAD4 genome AF: 0.0000550 AC: 6AN: 109054Hom.: 0 Cov.: 21 AF XY: 0.0000637 AC XY: 2AN XY: 31390
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at