rs1556026030

Positions:

• chrX-22099100-TCCCGCAGTA-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1 PM2 PM4

The NM_000444.6(PHEX):​c.1030_1038delCCGCAGTAC​(p.Pro344_Tyr346del) variant causes a conservative inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: PHEX NM_000444.6 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.17

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM1: In a disulfide_bond (size 264) in uniprot entity PHEX_HUMAN there are 5 pathogenic changes around while only 0 benign (100%) in NM_000444.6
• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_000444.6.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHEX	NM_000444.6	c.1030_1038delCCGCAGTAC	p.Pro344_Tyr346del	conservative_inframe_deletion	9/22	ENST00000379374.5	NP_000435.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHEX	ENST00000379374.5	c.1030_1038delCCGCAGTAC	p.Pro344_Tyr346del	conservative_inframe_deletion	9/22	1	NM_000444.6	ENSP00000368682.4
PHEX	ENST00000684143.1	c.1027_1035delCCGCAGTAC	p.Pro343_Tyr345del	conservative_inframe_deletion	9/11			ENSP00000508264.1
PHEX	ENST00000475778.2	n.1456_1464delCCGCAGTAC		non_coding_transcript_exon_variant	9/9	5
PHEX	ENST00000684745.1	n.704_712delCCGCAGTAC		non_coding_transcript_exon_variant	7/20

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: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Athena Diagnostics

Feb 08, 2017

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1556026030; hg19: chrX-22117218;