rs10521912

Positions:

• chrX-22058586-T-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PHEX	NM_000444.6	c.349+11375T>A		intron_variant		ENST00000379374.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHEX	ENST00000379374.5	c.349+11375T>A		intron_variant		1	NM_000444.6	P1
PHEX	ENST00000684143.1	c.349+11375T>A		intron_variant
PHEX	ENST00000475778.2	n.775+11375T>A		intron_variant, non_coding_transcript_variant		5
PHEX	ENST00000683214.1	n.545-18890T>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.147 AC: 16442 AN: 111624 Hom.: 1129 Cov.: 24 AF XY: 0.142 AC XY: 4790 AN XY: 33824

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

Gnomad4 AFR AF: 0.0349

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.186

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

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

Other links and lift over

dbSNP: rs10521912; hg19: chrX-22076704;