PXDN p.Pro371Pro

Variant names:

• chr2-1666391-G-G
• NM_012293.3:c.

Your query was ambiguous. Multiple possible variants found:

• chr2-1666392--
• chr2-1666392-C-A
• chr2-1666392-C-G
• chr2-1666392-C-T

Variant summary

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

The NM_012293.3(PXDN):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PXDN NM_012293.3 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.88
• Publications: 0 publications found

Genes affected

PXDN (HGNC:14966): (peroxidasin) This gene encodes a heme-containing peroxidase that is secreted into the extracellular matrix. It is involved in extracellular matrix formation, and may function in the physiological and pathological fibrogenic response in fibrotic kidney. Mutations in this gene cause corneal opacification and other ocular anomalies, and also microphthalmia and anterior segment dysgenesis. [provided by RefSeq, Aug 2014]

PXDN Gene-Disease associations (from GenCC):

• anterior segment dysgenesis 7

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012293.3. 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
	PXDN	NM_012293.3	MANE Select	c.		exon_region	Exon 10 of 23	NP_036425.1	Q92626-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PXDN	ENST00000252804.9	TSL:1 MANE Select	c.		exon_region	Exon 10 of 23	ENSP00000252804.4	Q92626-1
	PXDN	ENST00000433670.5	TSL:1	c.		exon_region	Exon 10 of 16	ENSP00000402738.1	H7C1W1
	PXDN	ENST00000857505.1		c.		exon_region	Exon 9 of 22	ENSP00000527564.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-6.9

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-1670163;