Variant X-22033061-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_000444.6(PHEX):c.56C>A(p.Thr19Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000456 in 1,097,599 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 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: 0.0000046 ( 0 hom. 1 hem. )

Consequence

PHEX
NM_000444.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.535

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18991157).

BP6

Variant X-22033061-C-A is Benign according to our data. Variant chrX-22033061-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2022925.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.56C>A	p.Thr19Asn	missense_variant	1/22	ENST00000379374.5	NP_000435.3
PHEX	NM_001282754.2 linkuse as main transcript	c.56C>A	p.Thr19Asn	missense_variant	1/21		NP_001269683.1
PHEX	XM_047442159.1 linkuse as main transcript	c.56C>A	p.Thr19Asn	missense_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.56C>A	p.Thr19Asn	missense_variant	1/22	1	NM_000444.6	ENSP00000368682	P1
PHEX	ENST00000684143.1 linkuse as main transcript	c.56C>A	p.Thr19Asn	missense_variant	1/11			ENSP00000508264
PHEX	ENST00000475778.2 linkuse as main transcript	n.482C>A		non_coding_transcript_exon_variant	1/9	5
PHEX	ENST00000683214.1 linkuse as main transcript	n.482C>A		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000546

AC:

AN:

183139

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67627

show subpopulations

Gnomad AFR exome

AF:

0.0000760

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000456

AC:

AN:

1097599

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

362953

show subpopulations

Gnomad4 AFR exome

AF:

0.000189

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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 08, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.44

CADD

Benign

5.6

DANN

Benign

0.74

DEOGEN2

Benign

0.26

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.68

M_CAP

Benign

0.046

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.19

REVEL

Benign

0.14

Sift

Benign

0.031

Sift4G

Benign

0.57

Polyphen

0.072

Vest4

0.44

MutPred

0.29

Loss of phosphorylation at T19 (P = 0.0966);

MVP

0.24

MPC

0.60

ClinPred

0.054

GERP RS

0.44

Varity_R

0.085

gMVP

0.67

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