rs41345546

Variant names:

• chrX-22401155-C-T
• rs41345546
• ENST00000683289.1:n.*28-24138C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000683289.1(PHEX):​n.*28-24138C>T variant causes a intron 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: PHEX ENST00000683289.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.753
• Publications: 0 publications found

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]

PTCHD1-AS (HGNC:37703): (PTCHD1 antisense RNA (head to head))

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PTCHD1-AS	NR_073010.2	n.454-11435G>A		intron_variant	Intron 4 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHEX	ENST00000683289.1	n.*28-24138C>T		intron_variant	Intron 11 of 13			ENSP00000508195.1
PTCHD1-AS	ENST00000687119.1	n.313-11435G>A		intron_variant	Intron 3 of 3
PTCHD1-AS	ENST00000687248.2	n.482-11435G>A		intron_variant	Intron 4 of 8

Frequencies

GnomAD3 genomes AF: 0.118 AC: 13084 AN: 111091 Hom.: 756 Cov.: 23

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

African (AFR) AF: 0.0294 AC: 902 AN: 30721

American (AMR) AF: 0.0949 AC: 989 AN: 10426

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 359 AN: 2629

East Asian (EAS) AF: 0.0404 AC: 143 AN: 3541

South Asian (SAS) AF: 0.206 AC: 539 AN: 2620

European-Finnish (FIN) AF: 0.133 AC: 784 AN: 5915

Middle Eastern (MID) AF: 0.163 AC: 35 AN: 215

European-Non Finnish (NFE) AF: 0.170 AC: 8990 AN: 52878

Other (OTH) AF: 0.131 AC: 200 AN: 1523

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
PhyloP100		-0.75

Splicing

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

Other links and lift over

dbSNP: rs41345546; hg19: chrX-22419272;