rs10521912

Variant names:

• chrX-22058586-T-A
• rs10521912
• NM_000444.6:c.349+11375T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000444.6(PHEX):​c.349+11375T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 111,680 control chromosomes in the GnomAD database, including 1,126 homozygotes. There are 4,798 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (1126 hom., 4798 hem., cov: 24)
• Consequence: PHEX NM_000444.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0590
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• X-linked dominant hypophosphatemic rickets

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHEX	NM_000444.6	c.349+11375T>A		intron_variant	Intron 3 of 21	ENST00000379374.5	NP_000435.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHEX	ENST00000379374.5	c.349+11375T>A		intron_variant	Intron 3 of 21	1	NM_000444.6	ENSP00000368682.4
PHEX	ENST00000684143.1	c.349+11375T>A		intron_variant	Intron 3 of 10			ENSP00000508264.1
PHEX	ENST00000475778.2	n.775+11375T>A		intron_variant	Intron 3 of 8	5
PHEX	ENST00000683214.1	n.545-18890T>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 16442 AN: 111624 Hom.: 1129 Cov.: 24

Gnomad AFR AF: 0.0350

Gnomad AMI AF: 0.0882

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.208

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.184

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.147 AC: 16443 AN: 111680 Hom.: 1126 Cov.: 24 AF XY: 0.142 AC XY: 4798 AN XY: 33888

African (AFR) AF: 0.0349 AC: 1080 AN: 30927

American (AMR) AF: 0.242 AC: 2533 AN: 10472

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 526 AN: 2647

East Asian (EAS) AF: 0.197 AC: 691 AN: 3512

South Asian (SAS) AF: 0.206 AC: 552 AN: 2674

European-Finnish (FIN) AF: 0.135 AC: 809 AN: 5986

Middle Eastern (MID) AF: 0.213 AC: 46 AN: 216

European-Non Finnish (NFE) AF: 0.186 AC: 9861 AN: 53037

Other (OTH) AF: 0.186 AC: 285 AN: 1529

Alfa AF: 0.160 Hom.: 940

Bravo AF: 0.158

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.67
PhyloP100		0.059
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10521912; hg19: chrX-22076704;