rs371934258

Variant names:

• chrX-22168377-A-G
• rs371934258
• NM_000444.6:c.1470A>G

Your query was ambiguous. Multiple possible variants found:

• chrX-22168377-A-G
• chrX-22168377-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000444.6(PHEX):​c.1470A>G​(p.Glu490Glu) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000892 in 112,111 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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 0.0000089 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: PHEX NM_000444.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.23
• Publications: 1 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))

PHEX-AS1 (HGNC:40445): (PHEX antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000444.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHEX	NM_000444.6	MANE Select	c.1470A>G	p.Glu490Glu	synonymous	Exon 13 of 22	NP_000435.3
	PHEX	NM_001282754.2		c.1470A>G	p.Glu490Glu	synonymous	Exon 13 of 21	NP_001269683.1
	PHEX-AS1	NR_046639.1		n.1267+1417T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHEX	ENST00000379374.5	TSL:1 MANE Select	c.1470A>G	p.Glu490Glu	synonymous	Exon 13 of 22	ENSP00000368682.4	P78562
	PHEX	ENST00000684356.1		c.24A>G	p.Glu8Glu	synonymous	Exon 3 of 12	ENSP00000507619.1	A0A804HJR7
	PHEX	ENST00000682888.1		c.24A>G	p.Glu8Glu	synonymous	Exon 2 of 8	ENSP00000508003.1	A0A804HKN7

Frequencies

GnomAD3 genomes AF: 0.00000892 AC: 1 AN: 112111 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1059250 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 328874

African (AFR) AF: 0.00 AC: 0 AN: 25710

American (AMR) AF: 0.00 AC: 0 AN: 35142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19135

East Asian (EAS) AF: 0.00 AC: 0 AN: 30022

South Asian (SAS) AF: 0.00 AC: 0 AN: 53246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40498

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3956

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 806787

Other (OTH) AF: 0.00 AC: 0 AN: 44754

GnomAD4 genome AF: 0.00000892 AC: 1 AN: 112111 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 34283

African (AFR) AF: 0.0000324 AC: 1 AN: 30861

American (AMR) AF: 0.00 AC: 0 AN: 10546

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2643

East Asian (EAS) AF: 0.00 AC: 0 AN: 3593

South Asian (SAS) AF: 0.00 AC: 0 AN: 2719

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6044

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53275

Other (OTH) AF: 0.00 AC: 0 AN: 1505

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	10
DANN	Benign	0.86
PhyloP100		5.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs371934258; hg19: chrX-22186494;