rs5951698

Variant names:

• chrX-22116540-A-G
• rs5951698
• NM_000444.6:c.1302+1954A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000444.6(PHEX):​c.1302+1954A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 111,565 control chromosomes in the GnomAD database, including 2,712 homozygotes. There are 4,399 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 0.14 (2712 hom., 4399 hem., cov: 23)
• Consequence: PHEX NM_000444.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83
• Publications: 4 publications found

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]

PHEX Gene-Disease associations (from GenCC):

• X-linked dominant hypophosphatemic rickets

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Illumina, Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000444.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHEX	NM_000444.6	MANE Select	c.1302+1954A>G		intron	N/A	NP_000435.3
	PHEX	NM_001282754.2		c.1302+1954A>G		intron	N/A	NP_001269683.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHEX	ENST00000379374.5	TSL:1 MANE Select	c.1302+1954A>G		intron	N/A	ENSP00000368682.4	P78562
	PHEX	ENST00000684745.1		n.976+1954A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.143 AC: 15981 AN: 111512 Hom.: 2704 Cov.: 23

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.00730

Gnomad AMR AF: 0.0652

Gnomad ASJ AF: 0.00604

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0290

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0556

Gnomad NFE AF: 0.00299

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.144 AC: 16019 AN: 111565 Hom.: 2712 Cov.: 23 AF XY: 0.130 AC XY: 4399 AN XY: 33823

African (AFR) AF: 0.490 AC: 14889 AN: 30412

American (AMR) AF: 0.0649 AC: 687 AN: 10584

Ashkenazi Jewish (ASJ) AF: 0.00604 AC: 16 AN: 2649

East Asian (EAS) AF: 0.00 AC: 0 AN: 3567

South Asian (SAS) AF: 0.0291 AC: 78 AN: 2681

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6065

Middle Eastern (MID) AF: 0.0566 AC: 12 AN: 212

European-Non Finnish (NFE) AF: 0.00297 AC: 158 AN: 53184

Other (OTH) AF: 0.114 AC: 174 AN: 1526

Alfa AF: 0.0772 Hom.: 5372

Bravo AF: 0.166

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	13
DANN	Benign	0.78
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5951698; hg19: chrX-22134658;