Variant rs73178792 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012293.3(PXDN):c.1946+6G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 1,606,026 control chromosomes in the GnomAD database, including 1,260 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.054 ( 656 hom., cov: 33)

Exomes 𝑓: 0.0063 ( 604 hom. )

Consequence

PXDN
NM_012293.3 splice_donor_region, intron

Scores

Splicing: ADA: 0.00003743

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.723

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 (BayesDel_noAF=-0.8).

BP6

Variant 2-1654394-C-T is Benign according to our data. Variant chr2-1654394-C-T is described in ClinVar as [Benign]. Clinvar id is 260221.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PXDN	NM_012293.3 linkuse as main transcript	c.1946+6G>A		splice_donor_region_variant, intron_variant		ENST00000252804.9	NP_036425.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
PXDN	ENST00000252804.9 linkuse as main transcript	c.1946+6G>A	splice_donor_region_variant, intron_variant	1	NM_012293.3	ENSP00000252804	P1	Q92626-1
PXDN	ENST00000433670.5 linkuse as main transcript	c.1933+6G>A	splice_donor_region_variant, intron_variant	1		ENSP00000402738
PXDN	ENST00000425171.2 linkuse as main transcript	c.1874+6G>A	splice_donor_region_variant, intron_variant	5		ENSP00000398363
PXDN	ENST00000478155.5 linkuse as main transcript	n.2538+6G>A	splice_donor_region_variant, intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0536

AC:

8151

AN:

152142

Hom.:

656

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0208

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.00788

Gnomad SAS

AF:

0.00622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.000926

Gnomad OTH

AF:

0.0545

GnomAD3 exomes

AF:

0.0149

AC:

3714

AN:

249004

Hom.:

296

AF XY:

0.0114

AC XY:

1546

AN XY:

135102

show subpopulations

Gnomad AFR exome

AF:

0.184

Gnomad AMR exome

AF:

0.0101

Gnomad ASJ exome

AF:

0.00995

Gnomad EAS exome

AF:

0.00607

Gnomad SAS exome

AF:

0.00458

Gnomad FIN exome

AF:

0.0000928

Gnomad NFE exome

AF:

0.000930

Gnomad OTH exome

AF:

0.00976

GnomAD4 exome

AF:

0.00629

AC:

9150

AN:

1453766

Hom.:

604

Cov.:

AF XY:

0.00550

AC XY:

3982

AN XY:

723414

show subpopulations

Gnomad4 AFR exome

AF:

0.186

Gnomad4 AMR exome

AF:

0.0118

Gnomad4 ASJ exome

AF:

0.0117

Gnomad4 EAS exome

AF:

0.00232

Gnomad4 SAS exome

AF:

0.00432

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000624

Gnomad4 OTH exome

AF:

0.0143

GnomAD4 genome

AF:

0.0537

AC:

8170

AN:

152260

Hom.:

656

Cov.:

AF XY:

0.0515

AC XY:

3832

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.182

Gnomad4 AMR

AF:

0.0207

Gnomad4 ASJ

AF:

0.0107

Gnomad4 EAS

AF:

0.00790

Gnomad4 SAS

AF:

0.00622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000926

Gnomad4 OTH

AF:

0.0545

Alfa

AF:

0.0247

Hom.:

145

Bravo

AF:

0.0606

Asia WGS

AF:

0.0240

AC:

AN:

3478

EpiCase

AF:

0.00104

EpiControl

AF:

0.00172

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 18, 2018	- -

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 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.86

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000037

dbscSNV1_RF

Benign

0.062

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