Variant X-22033049-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_000444.6(PHEX):c.44C>G(p.Ala15Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000283 in 1,097,100 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.000028 ( 0 hom. 9 hem. )

Consequence

PHEX
NM_000444.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.26

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 (HGNC:):

PHEX links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.19915733).

BP6

Variant X-22033049-C-G is Benign according to our data. Variant chrX-22033049-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2909415.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 9 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHEX	NM_000444.6 linkuse as main transcript	c.44C>G	p.Ala15Gly	missense_variant	1/22	ENST00000379374.5	NP_000435.3	P78562B4DWG8
PHEX	NM_001282754.2 linkuse as main transcript	c.44C>G	p.Ala15Gly	missense_variant	1/21		NP_001269683.1	P78562B4DNS0B4DWG8
PHEX	XM_047442159.1 linkuse as main transcript	c.44C>G	p.Ala15Gly	missense_variant	1/13		XP_047298115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PHEX	ENST00000379374.5 linkuse as main transcript	c.44C>G	p.Ala15Gly	missense_variant	1/22	1	NM_000444.6	ENSP00000368682.4	P78562
PHEX	ENST00000684143.1 linkuse as main transcript	c.44C>G	p.Ala15Gly	missense_variant	1/11			ENSP00000508264.1	A0A804HLA0
PHEX	ENST00000475778.2 linkuse as main transcript	n.470C>G		non_coding_transcript_exon_variant	1/9	5
PHEX	ENST00000683214.1 linkuse as main transcript	n.470C>G		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000164

AC:

AN:

183253

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67713

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000367

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000283

AC:

AN:

1097100

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

362490

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:

0.00

Gnomad4 NFE exome

AF:

0.0000369

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 30, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.27

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.72

M_CAP

Pathogenic

0.48

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.59

MutationAssessor

Benign

1.9

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.54

REVEL

Uncertain

0.29

Sift

Benign

0.049

Sift4G

Benign

0.16

Polyphen

0.037

Vest4

0.11

MutPred

0.12

Gain of disorder (P = 0.0798);

MVP

0.64

MPC

0.37

ClinPred

0.13

GERP RS

5.8

Varity_R

0.14

gMVP

0.47

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