Variant X-22168307-TG-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP6_ModerateBS2_Supporting

The NM_000444.6(PHEX):c.1405-4del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000393 in 1,171,661 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 hemizygotes in GnomAD. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.000039 ( 0 hom. 14 hem. )

Consequence

PHEX
NM_000444.6 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.836

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:

PHEX-AS1 (HGNC:40445): (PHEX antisense RNA 1)

PHEX-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

BP6

Variant X-22168307-TG-T is Benign according to our data. Variant chrX-22168307-TG-T is described in ClinVar as [Benign]. Clinvar id is 1559183.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 2 XL geneVariant has number of hemizygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHEX	NM_000444.6 linkuse as main transcript	c.1405-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000379374.5	NP_000435.3
PHEX-AS1	NR_046639.1 linkuse as main transcript	n.1267+1486del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHEX	ENST00000379374.5 linkuse as main transcript	c.1405-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000444.6	ENSP00000368682	P1
PHEX-AS1	ENST00000424650.1 linkuse as main transcript	n.1267+1486del		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000446

AC:

AN:

112143

Hom.:

Cov.:

AF XY:

0.0000583

AC XY:

AN XY:

34291

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000938

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000491

AC:

AN:

183168

Hom.:

AF XY:

0.0000738

AC XY:

AN XY:

67750

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000125

Gnomad NFE exome

AF:

0.0000734

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000387

AC:

AN:

1059518

Hom.:

Cov.:

AF XY:

0.0000421

AC XY:

AN XY:

332886

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000148

Gnomad4 NFE exome

AF:

0.0000421

Gnomad4 OTH exome

AF:

0.0000223

GnomAD4 genome

AF:

0.0000446

AC:

AN:

112143

Hom.:

Cov.:

AF XY:

0.0000583

AC XY:

AN XY:

34291

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000938

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000270

Hom.:

Bravo

AF:

0.0000189

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PHEX-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 14, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 17, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

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