Variant X-22032916-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000444.6(PHEX):c.-90A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 11464 hom., 16574 hem., cov: 22)

Exomes 𝑓: 0.46 ( 39380 hom. 81893 hem. )

Failed GnomAD Quality Control

Consequence

PHEX
NM_000444.6 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.55

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant X-22032916-A-G is Benign according to our data. Variant chrX-22032916-A-G is described in ClinVar as [Benign]. Clinvar id is 368155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
PHEX	NM_000444.6 linkuse as main transcript	c.-90A>G	5_prime_UTR_variant	1/22	ENST00000379374.5	NP_000435.3
PHEX	NM_001282754.2 linkuse as main transcript	c.-90A>G	5_prime_UTR_variant	1/21		NP_001269683.1
PHEX	XM_047442159.1 linkuse as main transcript	c.-90A>G	5_prime_UTR_variant	1/13		XP_047298115.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
PHEX	ENST00000379374.5 linkuse as main transcript	c.-90A>G	5_prime_UTR_variant	1/22	1	NM_000444.6	ENSP00000368682	P1
PHEX	ENST00000684143.1 linkuse as main transcript	c.-90A>G	5_prime_UTR_variant	1/11			ENSP00000508264
PHEX	ENST00000475778.2 linkuse as main transcript	n.337A>G	non_coding_transcript_exon_variant	1/9	5
PHEX	ENST00000683214.1 linkuse as main transcript	n.337A>G	non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes

AF:

0.524

AC:

57831

AN:

110312

Hom.:

11457

Cov.:

AF XY:

0.508

AC XY:

16533

AN XY:

32538

show subpopulations

Gnomad AFR

AF:

0.696

Gnomad AMI

AF:

0.371

Gnomad AMR

AF:

0.514

Gnomad ASJ

AF:

0.467

Gnomad EAS

AF:

0.362

Gnomad SAS

AF:

0.400

Gnomad FIN

AF:

0.419

Gnomad MID

AF:

0.437

Gnomad NFE

AF:

0.463

Gnomad OTH

AF:

0.495

GnomAD4 exome

AF:

0.461

AC:

247570

AN:

537030

Hom.:

39380

Cov.:

AF XY:

0.454

AC XY:

81893

AN XY:

180454

show subpopulations

Gnomad4 AFR exome

AF:

0.698

Gnomad4 AMR exome

AF:

0.522

Gnomad4 ASJ exome

AF:

0.459

Gnomad4 EAS exome

AF:

0.356

Gnomad4 SAS exome

AF:

0.394

Gnomad4 FIN exome

AF:

0.440

Gnomad4 NFE exome

AF:

0.463

Gnomad4 OTH exome

AF:

0.476

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.524

AC:

57880

AN:

110366

Hom.:

11464

Cov.:

AF XY:

0.508

AC XY:

16574

AN XY:

32602

show subpopulations

Gnomad4 AFR

AF:

0.696

Gnomad4 AMR

AF:

0.513

Gnomad4 ASJ

AF:

0.467

Gnomad4 EAS

AF:

0.362

Gnomad4 SAS

AF:

0.401

Gnomad4 FIN

AF:

0.419

Gnomad4 NFE

AF:

0.463

Gnomad4 OTH

AF:

0.499

Alfa

AF:

0.486

Hom.:

23088

Bravo

AF:

0.541

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Familial X-linked hypophosphatemic vitamin D refractory rickets

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.92

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