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rs7578605

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012293.3(PXDN):c.3953-14T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0641 in 1,613,794 control chromosomes in the GnomAD database, including 3,997 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.087 ( 726 hom., cov: 33)
Exomes 𝑓: 0.062 ( 3271 hom. )

Consequence

PXDN
NM_012293.3 splice_polypyrimidine_tract, intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.144
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
Variant 2-1639436-A-G is Benign according to our data. Variant chr2-1639436-A-G is described in ClinVar as [Benign]. Clinvar id is 260229.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-1639436-A-G is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PXDNNM_012293.3 linkuse as main transcriptc.3953-14T>C splice_polypyrimidine_tract_variant, intron_variant ENST00000252804.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PXDNENST00000252804.9 linkuse as main transcriptc.3953-14T>C splice_polypyrimidine_tract_variant, intron_variant 1 NM_012293.3 P1Q92626-1
PXDNENST00000453308.1 linkuse as main transcriptc.105-14T>C splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant 3
PXDNENST00000478155.5 linkuse as main transcriptn.3041-14T>C splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.0874
AC:
13298
AN:
152188
Hom.:
721
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.154
Gnomad AMI
AF:
0.0208
Gnomad AMR
AF:
0.0873
Gnomad ASJ
AF:
0.0421
Gnomad EAS
AF:
0.00789
Gnomad SAS
AF:
0.0159
Gnomad FIN
AF:
0.0503
Gnomad MID
AF:
0.0348
Gnomad NFE
AF:
0.0673
Gnomad OTH
AF:
0.0847
GnomAD3 exomes
AF:
0.0608
AC:
15140
AN:
249136
Hom.:
621
AF XY:
0.0559
AC XY:
7559
AN XY:
135156
show subpopulations
Gnomad AFR exome
AF:
0.158
Gnomad AMR exome
AF:
0.0872
Gnomad ASJ exome
AF:
0.0419
Gnomad EAS exome
AF:
0.00606
Gnomad SAS exome
AF:
0.0154
Gnomad FIN exome
AF:
0.0497
Gnomad NFE exome
AF:
0.0641
Gnomad OTH exome
AF:
0.0622
GnomAD4 exome
AF:
0.0617
AC:
90166
AN:
1461488
Hom.:
3271
Cov.:
33
AF XY:
0.0598
AC XY:
43505
AN XY:
727030
show subpopulations
Gnomad4 AFR exome
AF:
0.156
Gnomad4 AMR exome
AF:
0.0910
Gnomad4 ASJ exome
AF:
0.0428
Gnomad4 EAS exome
AF:
0.00282
Gnomad4 SAS exome
AF:
0.0154
Gnomad4 FIN exome
AF:
0.0520
Gnomad4 NFE exome
AF:
0.0645
Gnomad4 OTH exome
AF:
0.0606
GnomAD4 genome
AF:
0.0875
AC:
13326
AN:
152306
Hom.:
726
Cov.:
33
AF XY:
0.0851
AC XY:
6341
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.154
Gnomad4 AMR
AF:
0.0875
Gnomad4 ASJ
AF:
0.0421
Gnomad4 EAS
AF:
0.00791
Gnomad4 SAS
AF:
0.0157
Gnomad4 FIN
AF:
0.0503
Gnomad4 NFE
AF:
0.0673
Gnomad4 OTH
AF:
0.0843
Alfa
AF:
0.0671
Hom.:
738
Bravo
AF:
0.0919
Asia WGS
AF:
0.0290
AC:
103
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Anterior segment dysgenesis 7 Benign:2
Benign, criteria provided, single submitterclinical testingInvitaeJan 29, 2024- -
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabNov 07, 2021- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxAug 14, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.73
Cadd
Benign
0.39
Dann
Benign
0.63

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs7578605; hg19: chr2-1643208; API