rs2071201

Positions:

• chrX-22038014-C-T

Variant summary

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

The NM_000444.6(PHEX):​c.119-455C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 110,269 control chromosomes in the GnomAD database, including 2,561 homozygotes. There are 7,012 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 0.23 (2561 hom., 7012 hem., cov: 22)
• Consequence: PHEX NM_000444.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.221

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHEX	NM_000444.6	c.119-455C>T		intron_variant		ENST00000379374.5	NP_000435.3
PHEX	NM_001282754.2	c.119-455C>T		intron_variant			NP_001269683.1
PHEX	XM_047442159.1	c.119-455C>T		intron_variant			XP_047298115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHEX	ENST00000379374.5	c.119-455C>T		intron_variant		1	NM_000444.6	ENSP00000368682.4
PHEX	ENST00000684143.1	c.119-455C>T		intron_variant				ENSP00000508264.1
PHEX	ENST00000475778.2	n.545-455C>T		intron_variant		5
PHEX	ENST00000683214.1	n.544+4891C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.231 AC: 25486 AN: 110213 Hom.: 2557 Cov.: 22 AF XY: 0.215 AC XY: 6990 AN XY: 32497

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.231 AC: 25520 AN: 110269 Hom.: 2561 Cov.: 22 AF XY: 0.215 AC XY: 7012 AN XY: 32563

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.251

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.197

Alfa AF: 0.200 Hom.: 16012

Bravo AF: 0.233

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.47
DANN	Benign	0.38

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: rs2071201; hg19: chrX-22056132;