rs61747868

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_012293.3(PXDN):c.4088G>A(p.Gly1363Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00165 in 1,613,980 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0073 ( 14 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 15 hom. )

Consequence

PXDN
NM_012293.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.148

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=0.003169328).

BP6

Variant 2-1638964-C-T is Benign according to our data. Variant chr2-1638964-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 260230.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-1638964-C-T is described in Lovd as [Benign]. Variant chr2-1638964-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00726 (1106/152312) while in subpopulation AFR AF= 0.0244 (1016/41562). AF 95% confidence interval is 0.0232. There are 14 homozygotes in gnomad4. There are 532 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PXDN	NM_012293.3 link	c.4088G>A	p.Gly1363Glu	missense_variant	Exon 21 of 23	ENST00000252804.9	NP_036425.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PXDN	ENST00000252804.9 link	c.4088G>A	p.Gly1363Glu	missense_variant	Exon 21 of 23	1	NM_012293.3	ENSP00000252804.4	Q92626-1
PXDN	ENST00000478155.5 link	n.3176G>A		non_coding_transcript_exon_variant	Exon 13 of 15	2
PXDN	ENST00000453308.1 link	n.224+338G>A		intron_variant	Intron 2 of 3	3		ENSP00000414098.1	H7C3W2

Frequencies

GnomAD3 genomes

AF:

0.00723

AC:

1100

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00215

AC:

536

AN:

249244

Hom.:

AF XY:

0.00173

AC XY:

234

AN XY:

135222

show subpopulations

Gnomad AFR exome

AF:

0.0273

Gnomad AMR exome

AF:

0.00180

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000336

Gnomad OTH exome

AF:

0.000990

GnomAD4 exome

AF:

0.00106

AC:

1550

AN:

1461668

Hom.:

Cov.:

AF XY:

0.000983

AC XY:

715

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.0283

Gnomad4 AMR exome

AF:

0.00204

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000238

Gnomad4 OTH exome

AF:

0.00345

GnomAD4 genome

AF:

0.00726

AC:

1106

AN:

152312

Hom.:

Cov.:

AF XY:

0.00714

AC XY:

532

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0244

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00156

Hom.:

Bravo

AF:

0.00836

ESP6500AA

AF:

0.0225

AC:

ESP6500EA

AF:

0.000589

AC:

ExAC

AF:

0.00274

AC:

332

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Apr 14, 2023

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

See Variant Classification Assertion Criteria. -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Anterior segment dysgenesis 7

Benign:1

Oct 28, 2024

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

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.60

CADD

Benign

2.4

DANN

Benign

0.19

DEOGEN2

Benign

0.0094

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.37

MetaRNN

Benign

0.0032

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.22

REVEL

Benign

0.12

Sift

Benign

0.95

Sift4G

Benign

1.0

Polyphen

0.018

Vest4

0.22

MVP

0.17

MPC

0.53

ClinPred

0.0069

GERP RS

3.2

Varity_R

0.038

gMVP

0.23

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