Variant rs115076385 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_012293.3(PXDN):c.3198C>T(p.Ala1066Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 1,613,832 control chromosomes in the GnomAD database, including 162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0073 ( 3 hom., cov: 33)

Exomes 𝑓: 0.012 ( 159 hom. )

Consequence

PXDN
NM_012293.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.837

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:

PXDN (HGNC:):

PXDN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

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

BP6

Variant 2-1648582-G-A is Benign according to our data. Variant chr2-1648582-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 260226.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.837 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00733 (1117/152342) while in subpopulation SAS AF= 0.0211 (102/4830). AF 95% confidence interval is 0.0178. There are 3 homozygotes in gnomad4. There are 545 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 linkuse as main transcript	c.3198C>T	p.Ala1066Ala	synonymous_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.3198C>T	p.Ala1066Ala	synonymous_variant	17/23	1	NM_012293.3	ENSP00000252804.4		Q92626-1
PXDN	ENST00000478155.5 linkuse as main transcript	n.2697-3830C>T		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00733

AC:

1116

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00195

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00674

Gnomad ASJ

AF:

0.0144

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0209

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.0110

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.00910

AC:

2266

AN:

248934

Hom.:

AF XY:

0.0101

AC XY:

1361

AN XY:

135022

show subpopulations

Gnomad AFR exome

AF:

0.00186

Gnomad AMR exome

AF:

0.00397

Gnomad ASJ exome

AF:

0.0148

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.0227

Gnomad FIN exome

AF:

0.00112

Gnomad NFE exome

AF:

0.0105

Gnomad OTH exome

AF:

0.00776

GnomAD4 exome

AF:

0.0118

AC:

17273

AN:

1461490

Hom.:

159

Cov.:

AF XY:

0.0121

AC XY:

8833

AN XY:

727016

show subpopulations

Gnomad4 AFR exome

AF:

0.00149

Gnomad4 AMR exome

AF:

0.00434

Gnomad4 ASJ exome

AF:

0.0168

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0232

Gnomad4 FIN exome

AF:

0.00188

Gnomad4 NFE exome

AF:

0.0124

Gnomad4 OTH exome

AF:

0.0103

GnomAD4 genome

AF:

0.00733

AC:

1117

AN:

152342

Hom.:

Cov.:

AF XY:

0.00732

AC XY:

545

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00195

Gnomad4 AMR

AF:

0.00673

Gnomad4 ASJ

AF:

0.0144

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0211

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.0110

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00972

Hom.:

Bravo

AF:

0.00720

Asia WGS

AF:

0.00664

AC:

AN:

3478

EpiCase

AF:

0.0110

EpiControl

AF:

0.0122

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 11, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Anterior segment dysgenesis 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 18, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

6.2

DANN

Benign

0.69

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