rs2269466

Variant names:

• chrX-22137307-T-C
• rs2269466
• NM_000444.6:c.1404+3683T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000444.6(PHEX):​c.1404+3683T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 111,037 control chromosomes in the GnomAD database, including 2,521 homozygotes. There are 7,154 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (2521 hom., 7154 hem., cov: 22)
• Consequence: PHEX NM_000444.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.904

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHEX	NM_000444.6	c.1404+3683T>C		intron_variant	Intron 12 of 21	ENST00000379374.5	NP_000435.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHEX	ENST00000379374.5	c.1404+3683T>C		intron_variant	Intron 12 of 21	1	NM_000444.6	ENSP00000368682.4

Frequencies

GnomAD3 genomes AF: 0.224 AC: 24912 AN: 110985 Hom.: 2522 Cov.: 22 AF XY: 0.215 AC XY: 7149 AN XY: 33229

Gnomad AFR AF: 0.0551

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.254

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.224 AC: 24908 AN: 111037 Hom.: 2521 Cov.: 22 AF XY: 0.215 AC XY: 7154 AN XY: 33291

Gnomad4 AFR AF: 0.0550

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.252

Alfa AF: 0.288 Hom.: 15127

Bravo AF: 0.223

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.6
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2269466; hg19: chrX-22155424;