rs7891653

Positions:

• chrX-22307593-G-A

Variant summary

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

The NR_073010.2(PTCHD1-AS):​n.512-47751C>T 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 0.0396 in 111,475 control chromosomes in the GnomAD database, including 143 homozygotes. There are 1,308 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 0.040 (143 hom., 1308 hem., cov: 22)
• Consequence: PTCHD1-AS NR_073010.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.742

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTCHD1-AS	NR_073010.2	n.512-47751C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000687248.1	n.512-47751C>T		intron_variant, non_coding_transcript_variant
PHEX	ENST00000683289.1	c.625-47770G>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0396 AC: 4417 AN: 111422 Hom.: 143 Cov.: 22 AF XY: 0.0388 AC XY: 1304 AN XY: 33644

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0209

Gnomad ASJ AF: 0.0106

Gnomad EAS AF: 0.0419

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0138

Gnomad MID AF: 0.0167

Gnomad NFE AF: 0.00567

Gnomad OTH AF: 0.0353

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

GnomAD4 genome AF: 0.0396 AC: 4418 AN: 111475 Hom.: 143 Cov.: 22 AF XY: 0.0388 AC XY: 1308 AN XY: 33707

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.0208

Gnomad4 ASJ AF: 0.0106

Gnomad4 EAS AF: 0.0418

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.0138

Gnomad4 NFE AF: 0.00567

Gnomad4 OTH AF: 0.0381

Alfa AF: 0.0179 Hom.: 224

Bravo AF: 0.0422

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7891653; hg19: chrX-22325710;