chrX-22038014-C-T

Variant names:

• chrX-22038014-C-T
• rs2071201
• NM_000444.6:c.119-455C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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: Illumina, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PHEX	NM_000444.6	c.119-455C>T		intron_variant	Intron 1 of 21	ENST00000379374.5	NP_000435.3
PHEX	NM_001282754.2	c.119-455C>T		intron_variant	Intron 1 of 20		NP_001269683.1
PHEX	XM_047442159.1	c.119-455C>T		intron_variant	Intron 1 of 12		XP_047298115.1
PHEX	XM_024452390.2	c.-554C>T		upstream_gene_variant			XP_024308158.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHEX	ENST00000379374.5	c.119-455C>T		intron_variant	Intron 1 of 21	1	NM_000444.6	ENSP00000368682.4
PHEX	ENST00000684143.1	c.119-455C>T		intron_variant	Intron 1 of 10			ENSP00000508264.1
PHEX	ENST00000475778.2	n.545-455C>T		intron_variant	Intron 1 of 8	5
PHEX	ENST00000683214.1	n.544+4891C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 25486 AN: 110213 Hom.: 2557 Cov.: 22

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

African (AFR) AF: 0.362 AC: 10902 AN: 30147

American (AMR) AF: 0.120 AC: 1249 AN: 10378

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 582 AN: 2637

East Asian (EAS) AF: 0.251 AC: 874 AN: 3479

South Asian (SAS) AF: 0.208 AC: 539 AN: 2588

European-Finnish (FIN) AF: 0.161 AC: 938 AN: 5819

Middle Eastern (MID) AF: 0.193 AC: 41 AN: 212

European-Non Finnish (NFE) AF: 0.190 AC: 10010 AN: 52821

Other (OTH) AF: 0.197 AC: 297 AN: 1508

Alfa AF: 0.209 Hom.: 22584

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
PhyloP100		-0.22
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: rs2071201; hg19: chrX-22056132;