rs10521921

chrX-22490071-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.454-100351C>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 0.292 in 110,824 control chromosomes in the GnomAD database, including 5,672 homozygotes. There are 9,122 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 0.29 (5672 hom., 9122 hem., cov: 23)
• Consequence: PTCHD1-AS NR_073010.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTCHD1-AS	NR_073010.2	n.454-100351C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000687248.1	n.454-100351C>T		intron_variant, non_coding_transcript_variant
PHEX	ENST00000456621.1	n.291+167G>A		intron_variant, non_coding_transcript_variant		2
	ENST00000687119.1	n.313-100351C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.292 AC: 32363 AN: 110772 Hom.: 5668 Cov.: 23 AF XY: 0.275 AC XY: 9078 AN XY: 33036

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.0416

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.292 AC: 32412 AN: 110824 Hom.: 5672 Cov.: 23 AF XY: 0.276 AC XY: 9122 AN XY: 33098

Gnomad4 AFR AF: 0.670

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.0414

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.281

Alfa AF: 0.184 Hom.: 7418

Bravo AF: 0.315

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.086
Dann	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10521921; hg19: chrX-22508188;