rs41345546

Positions:

• chrX-22401155-C-T

Variant summary

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

The NR_073010.2(PTCHD1-AS):​n.454-11435G>A 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 0.118 in 111,143 control chromosomes in the GnomAD database, including 756 homozygotes. There are 3,809 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 0.12 (756 hom., 3809 hem., cov: 23)
• Consequence: PTCHD1-AS NR_073010.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.753

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 (SAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTCHD1-AS	NR_073010.2	n.454-11435G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000687248.1	n.454-11435G>A		intron_variant, non_coding_transcript_variant
PHEX	ENST00000683289.1	c.*28-24138C>T		intron_variant, NMD_transcript_variant				ENSP00000508195
	ENST00000687119.1	n.313-11435G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.118 AC: 13084 AN: 111091 Hom.: 756 Cov.: 23 AF XY: 0.114 AC XY: 3801 AN XY: 33319

Gnomad AFR AF: 0.0292

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.0951

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0405

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.118 AC: 13092 AN: 111143 Hom.: 756 Cov.: 23 AF XY: 0.114 AC XY: 3809 AN XY: 33381

Gnomad4 AFR AF: 0.0294

Gnomad4 AMR AF: 0.0949

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.0404

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.131

Alfa AF: 0.134 Hom.: 937

Bravo AF: 0.110

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.67
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs41345546; hg19: chrX-22419272;