rs202132697

Positions:

chr2-1648590-C-T

Variant summary

Our verdict is Benign. Variant got -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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as 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 criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 4.77

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 links:

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 (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]. Clinvar id is 217340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-1648590-C-T is described in Lovd as [Likely_benign]. Variant chr2-1648590-C-T is described in Lovd as [Benign].

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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PXDN	NM_012293.3 linkuse as main transcript	c.3190G>A	p.Ala1064Thr	missense_variant	17/23	ENST00000252804.9	NP_036425.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PXDN	ENST00000252804.9 linkuse as main transcript	c.3190G>A	p.Ala1064Thr	missense_variant	17/23	1	NM_012293.3	ENSP00000252804	P1	Q92626-1
PXDN	ENST00000478155.5 linkuse as main transcript	n.2697-3838G>A		intron_variant, non_coding_transcript_variant		2

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

GnomAD3 exomes

AF:

0.00183

AC:

455

AN:

248828

Hom.:

AF XY:

0.00179

AC XY:

242

AN XY:

134962

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 SAS exome

AF:

0.00193

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

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.000984

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.00252

Gnomad4 FIN exome

AF:

0.00218

Gnomad4 NFE exome

AF:

0.00275

Gnomad4 OTH exome

AF:

0.00253

GnomAD4 genome

AF:

0.00167

AC:

247

AN:

147952

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

107

AN XY:

72218

show subpopulations

Gnomad4 AFR

AF:

0.000299

Gnomad4 AMR

AF:

0.000538

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00282

Gnomad4 FIN

AF:

0.00301

Gnomad4 NFE

AF:

0.00270

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00204

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

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

PXDN-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 13, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Anterior segment dysgenesis 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 18, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 18, 2021

- -

Developmental cataract

Benign:1

Likely benign, no assertion criteria provided

research

Eye Genetics Research Group, Children's Medical Research Institute

Jan 09, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

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

MutationTaster

Benign

1.0

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

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over