Variant X-22033011-A-AGC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate

The NM_000444.6(PHEX):c.7_8dup(p.Glu4GlnfsTer29) variant causes a frameshift 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: 21)

Consequence

PHEX
NM_000444.6 frameshift

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 3.54

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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-22033011-A-AGC is Pathogenic according to our data. Variant chrX-22033011-A-AGC is described in ClinVar as [Pathogenic]. Clinvar id is 803735.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PHEX	NM_000444.6 linkuse as main transcript	c.7_8dup	p.Glu4GlnfsTer29	frameshift_variant	1/22	ENST00000379374.5	NP_000435.3
PHEX	NM_001282754.2 linkuse as main transcript	c.7_8dup	p.Glu4GlnfsTer29	frameshift_variant	1/21		NP_001269683.1
PHEX	XM_047442159.1 linkuse as main transcript	c.7_8dup	p.Glu4GlnfsTer29	frameshift_variant	1/13		XP_047298115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
PHEX	ENST00000379374.5 linkuse as main transcript	c.7_8dup	p.Glu4GlnfsTer29	frameshift_variant	1/22	1	NM_000444.6	ENSP00000368682	P1
PHEX	ENST00000684143.1 linkuse as main transcript	c.7_8dup	p.Glu4GlnfsTer29	frameshift_variant	1/11			ENSP00000508264
PHEX	ENST00000475778.2 linkuse as main transcript	n.433_434dup		non_coding_transcript_exon_variant	1/9	5
PHEX	ENST00000683214.1 linkuse as main transcript	n.433_434dup		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Familial X-linked hypophosphatemic vitamin D refractory rickets

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over