X-22129934-C-T

Variant names:

• chrX-22129934-C-T
• rs1540283
• NM_000444.6:c.1303-3589C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000444.6(PHEX):​c.1303-3589C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.76 (23051 hom., 24728 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: PHEX NM_000444.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.549
• Publications: 3 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHEX	NM_000444.6	c.1303-3589C>T		intron_variant	Intron 11 of 21	ENST00000379374.5	NP_000435.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHEX	ENST00000379374.5	c.1303-3589C>T		intron_variant	Intron 11 of 21	1	NM_000444.6	ENSP00000368682.4
PHEX	ENST00000684745.1	n.977-3589C>T		intron_variant	Intron 9 of 19

Frequencies

GnomAD3 genomes AF: 0.761 AC: 83824 AN: 110173 Hom.: 23052 Cov.: 22

Gnomad AFR AF: 0.943

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.783

Gnomad SAS AF: 0.797

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.732

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.761 AC: 83879 AN: 110226 Hom.: 23051 Cov.: 22 AF XY: 0.762 AC XY: 24728 AN XY: 32454

African (AFR) AF: 0.943 AC: 28593 AN: 30329

American (AMR) AF: 0.745 AC: 7673 AN: 10305

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 1627 AN: 2641

East Asian (EAS) AF: 0.783 AC: 2726 AN: 3481

South Asian (SAS) AF: 0.798 AC: 2070 AN: 2595

European-Finnish (FIN) AF: 0.747 AC: 4266 AN: 5711

Middle Eastern (MID) AF: 0.565 AC: 121 AN: 214

European-Non Finnish (NFE) AF: 0.668 AC: 35281 AN: 52794

Other (OTH) AF: 0.733 AC: 1094 AN: 1492

Alfa AF: 0.707 Hom.: 61869

Bravo AF: 0.768

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.20
DANN	Benign	0.54
PhyloP100		-0.55
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: rs1540283; hg19: chrX-22148051;