chr12-4368957-GGAA-G
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2
The NM_020638.3(FGF23):c.*1383_*1385del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0013 in 225,350 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0015 ( 2 hom., cov: 31)
Exomes 𝑓: 0.00088 ( 0 hom. )
Consequence
FGF23
NM_020638.3 3_prime_UTR
NM_020638.3 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.321
Genes affected
FGF23 (HGNC:3680): (fibroblast growth factor 23) This gene encodes a member of the fibroblast growth factor family of proteins, which possess broad mitogenic and cell survival activities and are involved in a variety of biological processes. The product of this gene regulates phosphate homeostasis and transport in the kidney. The full-length, functional protein may be deactivated via cleavage into N-terminal and C-terminal chains. Mutation of this cleavage site causes autosomal dominant hypophosphatemic rickets (ADHR). Mutations in this gene are also associated with hyperphosphatemic familial tumoral calcinosis (HFTC). [provided by RefSeq, Feb 2013]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00151 (230/152222) while in subpopulation AFR AF= 0.00433 (180/41532). AF 95% confidence interval is 0.00382. There are 2 homozygotes in gnomad4. There are 113 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High Homozygotes in GnomAd4 at 2 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FGF23 | NM_020638.3 | c.*1383_*1385del | 3_prime_UTR_variant | 3/3 | ENST00000237837.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FGF23 | ENST00000237837.2 | c.*1383_*1385del | 3_prime_UTR_variant | 3/3 | 1 | NM_020638.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00151 AC: 230AN: 152106Hom.: 2 Cov.: 31
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GnomAD4 exome AF: 0.000875 AC: 64AN: 73128Hom.: 0 AF XY: 0.000679 AC XY: 23AN XY: 33864
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GnomAD4 genome AF: 0.00151 AC: 230AN: 152222Hom.: 2 Cov.: 31 AF XY: 0.00152 AC XY: 113AN XY: 74426
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Familial hyperphosphatemic tumoral calcinosis/hyperphosphatemic hyperostosis syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Hypophosphatemic Rickets, Dominant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at