X-22032992-CTACGGCCCTTCTGATGGAAGC-TGGGAGCAGCGTGG

Variant names:

• chrX-22032992-CTACGGCCCTTCTGATGGAAGC-TGGGAGCAGCGTGG
• NM_000444.6:c.-14_8delCTACGGCCCTTCTGATGGAAGCinsTGGGAGCAGCGTGG

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_Strong PM2 PP5_Moderate

The NM_000444.6(PHEX):​c.-14_8delCTACGGCCCTTCTGATGGAAGCinsTGGGAGCAGCGTGG​(p.Met1fs) variant causes a frameshift, start lost, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: PHEX NM_000444.6 frameshift, start_lost, synonymous
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 3.36

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 Likely_pathogenic. Variant got 8 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 16 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-22032992-CTACGGCCCTTCTGATGGAAGC-TGGGAGCAGCGTGG is Pathogenic according to our data. Variant chrX-22032992-CTACGGCCCTTCTGATGGAAGC-TGGGAGCAGCGTGG is described in ClinVar as [Pathogenic]. Clinvar id is 3765335.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHEX	NM_000444.6	c.-14_8delCTACGGCCCTTCTGATGGAAGCinsTGGGAGCAGCGTGG	p.Met1fs	frameshift_variant, start_lost, synonymous_variant	Exon 1 of 22	ENST00000379374.5	NP_000435.3
PHEX	NM_000444.6	c.-14_8delCTACGGCCCTTCTGATGGAAGCinsTGGGAGCAGCGTGG		5_prime_UTR_variant	Exon 1 of 22	ENST00000379374.5	NP_000435.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHEX	ENST00000379374.5	c.-14_8delCTACGGCCCTTCTGATGGAAGCinsTGGGAGCAGCGTGG	p.Met1fs	frameshift_variant, start_lost, synonymous_variant	Exon 1 of 22	1	NM_000444.6	ENSP00000368682.4
PHEX	ENST00000379374	c.-14_8delCTACGGCCCTTCTGATGGAAGCinsTGGGAGCAGCGTGG		5_prime_UTR_variant	Exon 1 of 22	1	NM_000444.6	ENSP00000368682.4

Frequencies

GnomAD3 genomes Cov.: 22

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

GnomAD4 genome Cov.: 22

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Pathogenic:1

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-22051110;