rs6752525

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012293.3(PXDN):c.3093C>T(p.Tyr1031Tyr) variant causes a synonymous change. The variant allele was found at a frequency of 0.00689 in 1,607,828 control chromosomes in the GnomAD database, including 581 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 295 hom., cov: 32)

Exomes 𝑓: 0.0039 ( 286 hom. )

Consequence

PXDN
NM_012293.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.08

Publications

1 publications found

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]

PXDN Gene-Disease associations (from GenCC):

anterior segment dysgenesis 7
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, PanelApp Australia, ClinGen, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

PXDN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 2-1648687-G-A is Benign according to our data. Variant chr2-1648687-G-A is described in ClinVar as Benign. ClinVar VariationId is 260225.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PXDN	NM_012293.3 link	c.3093C>T	p.Tyr1031Tyr	synonymous_variant	Exon 17 of 23	ENST00000252804.9	NP_036425.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PXDN	ENST00000252804.9 link	c.3093C>T	p.Tyr1031Tyr	synonymous_variant	Exon 17 of 23	1	NM_012293.3	ENSP00000252804.4
PXDN	ENST00000478155.5 link	n.2697-3935C>T		intron_variant	Intron 9 of 14	2

Frequencies

GnomAD3 genomes

AF:

0.0352

AC:

5349

AN:

152114

Hom.:

295

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0139

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00814

Gnomad SAS

AF:

0.00580

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.0335

GnomAD2 exomes

AF:

0.00974

AC:

2311

AN:

237238

AF XY:

0.00771

show subpopulations

Gnomad AFR exome

AF:

0.127

Gnomad AMR exome

AF:

0.00604

Gnomad ASJ exome

AF:

0.000204

Gnomad EAS exome

AF:

0.00602

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000270

Gnomad OTH exome

AF:

0.00597

GnomAD4 exome

AF:

0.00393

AC:

5717

AN:

1455596

Hom.:

286

Cov.:

AF XY:

0.00349

AC XY:

2528

AN XY:

723424

show subpopulations

African (AFR)

AF:

0.125

AC:

4180

AN:

33330

American (AMR)

AF:

0.00694

AC:

305

AN:

43976

Ashkenazi Jewish (ASJ)

AF:

0.0000385

AC:

AN:

25994

East Asian (EAS)

AF:

0.00231

AC:

AN:

39410

South Asian (SAS)

AF:

0.00410

AC:

348

AN:

84914

European-Finnish (FIN)

AF:

0.0000190

AC:

AN:

52500

Middle Eastern (MID)

AF:

0.00694

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000199

AC:

221

AN:

1109548

Other (OTH)

AF:

0.00881

AC:

530

AN:

60160

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

432

864

1295

1727

2159

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

142

284

426

568

710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0352

AC:

5364

AN:

152232

Hom.:

295

Cov.:

AF XY:

0.0342

AC XY:

2544

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.120

AC:

4980

AN:

41514

American (AMR)

AF:

0.0138

AC:

212

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00816

AC:

AN:

5150

South Asian (SAS)

AF:

0.00580

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000412

AC:

AN:

68030

Other (OTH)

AF:

0.0336

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

237

474

710

947

1184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0161

Hom.:

Bravo

AF:

0.0400

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 31, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Anterior segment dysgenesis 7

Benign:1

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

4.4

(source)

DANN

Benign

0.56

PhyloP100

4.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over