Variant 2-1648959-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_012293.3(PXDN):c.2821G>A(p.Val941Met) variant causes a missense change. The variant allele was found at a frequency of 0.00404 in 1,607,360 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0041 ( 18 hom. )

Consequence

PXDN
NM_012293.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.91

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009365916).

BP6

Variant 2-1648959-C-T is Benign according to our data. Variant chr2-1648959-C-T is described in ClinVar as [Benign]. Clinvar id is 471913.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00347 (528/152146) while in subpopulation NFE AF= 0.00505 (343/67980). AF 95% confidence interval is 0.00461. There are 3 homozygotes in gnomad4. There are 260 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PXDN	NM_012293.3 link	c.2821G>A	p.Val941Met	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 link	c.2821G>A	p.Val941Met	missense_variant	17/23	1	NM_012293.3	ENSP00000252804.4		Q92626-1
PXDN	ENST00000478155.5 link	n.2697-4207G>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00347

AC:

528

AN:

152026

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000749

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00505

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00352

AC:

829

AN:

235778

Hom.:

AF XY:

0.00349

AC XY:

453

AN XY:

129842

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.000323

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000931

Gnomad FIN exome

AF:

0.0118

Gnomad NFE exome

AF:

0.00489

Gnomad OTH exome

AF:

0.00312

GnomAD4 exome

AF:

0.00410

AC:

5966

AN:

1455214

Hom.:

Cov.:

AF XY:

0.00389

AC XY:

2816

AN XY:

723238

show subpopulations

Gnomad4 AFR exome

AF:

0.000899

Gnomad4 AMR exome

AF:

0.000517

Gnomad4 ASJ exome

AF:

0.0000385

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00105

Gnomad4 FIN exome

AF:

0.0112

Gnomad4 NFE exome

AF:

0.00459

Gnomad4 OTH exome

AF:

0.00250

GnomAD4 genome

AF:

0.00347

AC:

528

AN:

152146

Hom.:

Cov.:

AF XY:

0.00350

AC XY:

260

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.000747

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0132

Gnomad4 NFE

AF:

0.00505

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00295

Hom.:

Bravo

AF:

0.00260

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.000788

AC:

ESP6500EA

AF:

0.00500

AC:

ExAC

AF:

0.00359

AC:

425

EpiCase

AF:

0.00344

EpiControl

AF:

0.00297

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Anterior segment dysgenesis 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.020

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.96

MetaRNN

Benign

0.0094

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.6

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.75

REVEL

Benign

0.14

Sift

Benign

0.22

Sift4G

Benign

0.19

Polyphen

0.64

Vest4

0.51

MVP

0.71

MPC

0.70

ClinPred

0.011

GERP RS

4.7

Varity_R

0.12

gMVP

0.56

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