rs202132697

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_012293.3(PXDN):c.3190G>A(p.Ala1064Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00239 in 1,609,374 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0025 ( 7 hom. )

Consequence

PXDN
NM_012293.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 4.77

Publications

9 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: ClinGen, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet

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 (MetaRNN=0.034437597).

BP6

Variant 2-1648590-C-T is Benign according to our data. Variant chr2-1648590-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 217340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00167 (247/147952) while in subpopulation SAS AF = 0.00282 (13/4602). AF 95% confidence interval is 0.00238. There are 0 homozygotes in GnomAd4. There are 107 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

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.3190G>A	p.Ala1064Thr	missense	Exon 17 of 23	NP_036425.1	Q92626-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PXDN	ENST00000252804.9	TSL:1 MANE Select	c.3190G>A	p.Ala1064Thr	missense	Exon 17 of 23	ENSP00000252804.4	Q92626-1
PXDN	ENST00000857505.1		c.3118G>A	p.Ala1040Thr	missense	Exon 16 of 22	ENSP00000527564.1
PXDN	ENST00000478155.5	TSL:2	n.2697-3838G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00167

AC:

247

AN:

147820

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000300

Gnomad AMI

AF:

0.00335

Gnomad AMR

AF:

0.000538

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00282

Gnomad FIN

AF:

0.00301

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00270

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00183

AC:

455

AN:

248828

AF XY:

0.00179

show subpopulations

Gnomad AFR exome

AF:

0.000321

Gnomad AMR exome

AF:

0.000783

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad FIN exome

AF:

0.00262

Gnomad NFE exome

AF:

0.00265

Gnomad OTH exome

AF:

0.00116

GnomAD4 exome

AF:

0.00247

AC:

3605

AN:

1461422

Hom.:

Cov.:

AF XY:

0.00251

AC XY:

1827

AN XY:

726974

show subpopulations

African (AFR)

AF:

0.000329

AC:

AN:

33478

American (AMR)

AF:

0.000984

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.000176

AC:

AN:

39698

South Asian (SAS)

AF:

0.00252

AC:

217

AN:

86218

European-Finnish (FIN)

AF:

0.00218

AC:

116

AN:

53206

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00275

AC:

3054

AN:

1111834

Other (OTH)

AF:

0.00253

AC:

153

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

277

554

832

1109

1386

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

122

244

366

488

610

<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:

0.00167

AC:

247

AN:

147952

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

107

AN XY:

72218

show subpopulations

African (AFR)

AF:

0.000299

AC:

AN:

40100

American (AMR)

AF:

0.000538

AC:

AN:

14882

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3446

East Asian (EAS)

AF:

0.00

AC:

AN:

4742

South Asian (SAS)

AF:

0.00282

AC:

AN:

4602

European-Finnish (FIN)

AF:

0.00301

AC:

AN:

10298

Middle Eastern (MID)

AF:

0.00

AC:

AN:

234

European-Non Finnish (NFE)

AF:

0.00270

AC:

180

AN:

66716

Other (OTH)

AF:

0.00

AC:

AN:

2036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00208

Hom.:

Bravo

AF:

0.00146

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00361

AC:

ExAC

AF:

0.00189

AC:

230

EpiCase

AF:

0.00213

EpiControl

AF:

0.00267

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Anterior segment dysgenesis 7 (1)

Developmental cataract (1)

PXDN-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.056

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.042

MetaRNN

Benign

0.034

MetaSVM

Benign

-0.45

MutationAssessor

Benign

2.0

PhyloP100

4.8

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.6

REVEL

Benign

0.21

Sift

Benign

0.11

Sift4G

Benign

0.11

Polyphen

0.86

Vest4

0.56

MVP

0.85

MPC

1.0

ClinPred

0.052

GERP RS

5.7

Varity_R

0.30

gMVP

0.82

Mutation Taster

=65/35

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over