rs3832879

Positions:

• chr12-4372733-C-CA
• chr12-4372733-C-CG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020638.3(FGF23):​c.212-37_212-36insT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000418 in 1,194,768 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: FGF23 NM_020638.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

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]

ENSG00000285901 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGF23	NM_020638.3	c.212-37_212-36insT		intron_variant		ENST00000237837.2	NP_065689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGF23	ENST00000237837.2	c.212-37_212-36insT		intron_variant		1	NM_020638.3	ENSP00000237837.1
ENSG00000285901	ENST00000674624.1	n.*1204+6451_*1204+6452insA		intron_variant				ENSP00000501898.1
FGF23	ENST00000648269.1	n.1675_1676insT		non_coding_transcript_exon_variant	1/2
ENSG00000285901	ENST00000648100.1	n.*1967+6451_*1967+6452insA		intron_variant				ENSP00000497536.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 249886 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135258

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000418 AC: 5 AN: 1194768 Hom.: 0 Cov.: 17 AF XY: 0.00000494 AC XY: 3 AN XY: 607352

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000247

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000230

Gnomad4 OTH exome AF: 0.0000194

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BranchPoint Hunter		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3832879; hg19: chr12-4481899;