rs5951698

chrX-22116540-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHEX	NM_000444.6	c.1302+1954A>G		intron_variant		ENST00000379374.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHEX	ENST00000379374.5	c.1302+1954A>G		intron_variant		1	NM_000444.6	P1
PHEX	ENST00000684745.1	n.976+1954A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.143 AC: 15981 AN: 111512 Hom.: 2704 Cov.: 23 AF XY: 0.130 AC XY: 4372 AN XY: 33760

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

Gnomad4 AFR AF: 0.490

Gnomad4 AMR AF: 0.0649

Gnomad4 ASJ AF: 0.00604

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0291

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00297

Gnomad4 OTH AF: 0.114

Alfa AF: 0.0307 Hom.: 1383

Bravo AF: 0.166

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	13
Dann	Benign	0.78

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: rs5951698; hg19: chrX-22134658;