rs7891653

Variant names:

• chrX-22307593-G-A
• rs7891653
• ENST00000683289.1:n.625-47770G>A

Variant summary

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

The ENST00000683289.1(PHEX):​n.625-47770G>A variant causes a intron 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: PHEX ENST00000683289.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.742
• 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=-0.91).
• 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 rank	MANE	Protein	UniProt
PTCHD1-AS	NR_073010.2	n.512-47751C>T		intron_variant	Intron 5 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHEX	ENST00000683289.1	n.625-47770G>A		intron_variant	Intron 9 of 13			ENSP00000508195.1
PTCHD1-AS	ENST00000687248.2	n.540-47751C>T		intron_variant	Intron 5 of 8
PTCHD1-AS	ENST00000715857.1	n.60-49630C>T		intron_variant	Intron 1 of 6

Frequencies

GnomAD3 genomes AF: 0.0396 AC: 4417 AN: 111422 Hom.: 143 Cov.: 22

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

African (AFR) AF: 0.106 AC: 3231 AN: 30619

American (AMR) AF: 0.0208 AC: 220 AN: 10562

Ashkenazi Jewish (ASJ) AF: 0.0106 AC: 28 AN: 2638

East Asian (EAS) AF: 0.0418 AC: 148 AN: 3543

South Asian (SAS) AF: 0.132 AC: 346 AN: 2616

European-Finnish (FIN) AF: 0.0138 AC: 83 AN: 6027

Middle Eastern (MID) AF: 0.0138 AC: 3 AN: 218

European-Non Finnish (NFE) AF: 0.00567 AC: 301 AN: 53046

Other (OTH) AF: 0.0381 AC: 58 AN: 1522

Alfa AF: 0.0203 Hom.: 284

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
PhyloP100		-0.74

Splicing

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

Other links and lift over

dbSNP: rs7891653; hg19: chrX-22325710;