rs558163499
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_012293.3(PXDN):c.2568delC(p.Cys857AlafsTer5) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000366 in 1,364,368 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000037 ( 0 hom. )
Consequence
PXDN
NM_012293.3 frameshift
NM_012293.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.770
Publications
4 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 7Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, PanelApp Australia, ClinGen, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 2-1649211-AG-A is Pathogenic according to our data. Variant chr2-1649211-AG-A is described in ClinVar as Pathogenic. ClinVar VariationId is 140741.Status of the report is no_assertion_criteria_provided, 0 stars.
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
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PXDN | NM_012293.3 | MANE Select | c.2568delC | p.Cys857AlafsTer5 | frameshift | Exon 17 of 23 | NP_036425.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PXDN | ENST00000252804.9 | TSL:1 MANE Select | c.2568delC | p.Cys857AlafsTer5 | frameshift | Exon 17 of 23 | ENSP00000252804.4 | ||
| PXDN | ENST00000478155.5 | TSL:2 | n.2696+4416delC | intron | N/A | ||||
| PXDN | ENST00000465809.1 | TSL:4 | n.*153delC | downstream_gene | N/A |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000366 AC: 5AN: 1364368Hom.: 0 Cov.: 77 AF XY: 0.00000294 AC XY: 2AN XY: 679514 show subpopulations
GnomAD4 exome
AF:
AC:
5
AN:
1364368
Hom.:
Cov.:
77
AF XY:
AC XY:
2
AN XY:
679514
show subpopulations
African (AFR)
AF:
AC:
0
AN:
30870
American (AMR)
AF:
AC:
0
AN:
42230
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
22358
East Asian (EAS)
AF:
AC:
0
AN:
29602
South Asian (SAS)
AF:
AC:
0
AN:
85020
European-Finnish (FIN)
AF:
AC:
3
AN:
46538
Middle Eastern (MID)
AF:
AC:
0
AN:
5284
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1048432
Other (OTH)
AF:
AC:
0
AN:
54034
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.395
Heterozygous variant carriers
0
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2
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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10
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30-35
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Anterior segment dysgenesis 7 Pathogenic:1
Sep 09, 2011
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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