rs3811613

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_012293.3(PXDN):c.2892C>T(p.Asn964Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 1,601,446 control chromosomes in the GnomAD database, including 67,217 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 4947 hom., cov: 32)

Exomes 𝑓: 0.29 ( 62270 hom. )

Consequence

PXDN
NM_012293.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0450

Publications

16 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 -21 ACMG points.

BP4

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

BP6

Variant 2-1648888-G-A is Benign according to our data. Variant chr2-1648888-G-A is described in ClinVar as [Benign]. Clinvar id is 260224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.045 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PXDN	NM_012293.3 link	c.2892C>T	p.Asn964Asn	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.2892C>T	p.Asn964Asn	synonymous_variant	Exon 17 of 23	1	NM_012293.3	ENSP00000252804.4		Q92626-1
PXDN	ENST00000478155.5 link	n.2697-4136C>T		intron_variant	Intron 9 of 14	2

Frequencies

GnomAD3 genomes

AF:

0.246

AC:

37341

AN:

151770

Hom.:

4951

Cov.:

show subpopulations

Gnomad AFR

AF:

0.147

Gnomad AMI

AF:

0.235

Gnomad AMR

AF:

0.241

Gnomad ASJ

AF:

0.273

Gnomad EAS

AF:

0.270

Gnomad SAS

AF:

0.310

Gnomad FIN

AF:

0.239

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.301

Gnomad OTH

AF:

0.242

GnomAD2 exomes

AF:

0.278

AC:

64544

AN:

232446

AF XY:

0.284

show subpopulations

Gnomad AFR exome

AF:

0.142

Gnomad AMR exome

AF:

0.236

Gnomad ASJ exome

AF:

0.282

Gnomad EAS exome

AF:

0.269

Gnomad FIN exome

AF:

0.252

Gnomad NFE exome

AF:

0.301

Gnomad OTH exome

AF:

0.290

GnomAD4 exome

AF:

0.292

AC:

422585

AN:

1449558

Hom.:

62270

Cov.:

AF XY:

0.294

AC XY:

211512

AN XY:

720626

show subpopulations

African (AFR)

AF:

0.144

AC:

4797

AN:

33400

American (AMR)

AF:

0.233

AC:

10300

AN:

44176

Ashkenazi Jewish (ASJ)

AF:

0.282

AC:

7338

AN:

25994

East Asian (EAS)

AF:

0.259

AC:

10246

AN:

39510

South Asian (SAS)

AF:

0.318

AC:

27242

AN:

85644

European-Finnish (FIN)

AF:

0.258

AC:

11869

AN:

46044

Middle Eastern (MID)

AF:

0.336

AC:

1933

AN:

5754

European-Non Finnish (NFE)

AF:

0.299

AC:

331608

AN:

1108956

Other (OTH)

AF:

0.287

AC:

17252

AN:

60080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

21858

43716

65573

87431

109289

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10874

21748

32622

43496

54370

<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:

0.246

AC:

37332

AN:

151888

Hom.:

4947

Cov.:

AF XY:

0.244

AC XY:

18084

AN XY:

74202

show subpopulations

African (AFR)

AF:

0.146

AC:

6061

AN:

41456

American (AMR)

AF:

0.241

AC:

3684

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.273

AC:

948

AN:

3472

East Asian (EAS)

AF:

0.270

AC:

1366

AN:

5064

South Asian (SAS)

AF:

0.311

AC:

1493

AN:

4808

European-Finnish (FIN)

AF:

0.239

AC:

2524

AN:

10558

Middle Eastern (MID)

AF:

0.306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.301

AC:

20437

AN:

67916

Other (OTH)

AF:

0.243

AC:

515

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1418

2836

4253

5671

7089

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

412

824

1236

1648

2060

<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:

0.284

Hom.:

12282

Bravo

AF:

0.241

Asia WGS

AF:

0.295

AC:

1026

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Anterior segment dysgenesis 7

Benign:2

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 01, 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. -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

0.80

PhyloP100

0.045

Mutation Taster

=96/4

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