rs4828840

Positions:

• chrX-22486134-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_073010.2(PTCHD1-AS):​n.454-96414T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 110,532 control chromosomes in the GnomAD database, including 2,656 homozygotes. There are 6,723 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 0.22 (2656 hom., 6723 hem., cov: 22)
• Consequence: PTCHD1-AS NR_073010.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.449

Genes affected

(HGNC:):

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTCHD1-AS	NR_073010.2	n.454-96414T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000687248.1	n.454-96414T>C		intron_variant, non_coding_transcript_variant
PHEX	ENST00000456621.1	n.235-3714A>G		intron_variant, non_coding_transcript_variant		2
	ENST00000687119.1	n.313-96414T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.224 AC: 24754 AN: 110497 Hom.: 2656 Cov.: 22 AF XY: 0.205 AC XY: 6712 AN XY: 32797

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.0775

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.173

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.224 AC: 24759 AN: 110532 Hom.: 2656 Cov.: 22 AF XY: 0.205 AC XY: 6723 AN XY: 32844

Gnomad4 AFR AF: 0.416

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.0771

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.221

Alfa AF: 0.198 Hom.: 1275

Bravo AF: 0.242

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4828840; hg19: chrX-22504251;