Variant chr2-1633876-T-C 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.*328A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 195,932 control chromosomes in the GnomAD database, including 28,312 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 20993 hom., cov: 31)

Exomes 𝑓: 0.57 ( 7319 hom. )

Consequence

PXDN
NM_012293.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.116

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=-0.75).

BP6

Variant 2-1633876-T-C is Benign according to our data. Variant chr2-1633876-T-C is described in ClinVar as [Benign]. Clinvar id is 1181985.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.6 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.*328A>G		3_prime_UTR_variant	23/23	ENST00000252804.9	NP_036425.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PXDN	ENST00000252804.9 linkuse as main transcript	c.*328A>G	3_prime_UTR_variant	23/23	1	NM_012293.3	ENSP00000252804	P1	Q92626-1
PXDN	ENST00000493654.1 linkuse as main transcript	n.2105A>G	non_coding_transcript_exon_variant	2/2	2
PXDN	ENST00000453308.1 linkuse as main transcript		downstream_gene_variant		3		ENSP00000414098
PXDN	ENST00000478155.5 linkuse as main transcript		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.511

AC:

77523

AN:

151632

Hom.:

21007

Cov.:

show subpopulations

Gnomad AFR

AF:

0.319

Gnomad AMI

AF:

0.699

Gnomad AMR

AF:

0.473

Gnomad ASJ

AF:

0.557

Gnomad EAS

AF:

0.595

Gnomad SAS

AF:

0.596

Gnomad FIN

AF:

0.596

Gnomad MID

AF:

0.674

Gnomad NFE

AF:

0.605

Gnomad OTH

AF:

0.536

GnomAD4 exome

AF:

0.566

AC:

24984

AN:

44178

Hom.:

7319

Cov.:

AF XY:

0.565

AC XY:

12802

AN XY:

22650

show subpopulations

Gnomad4 AFR exome

AF:

0.313

Gnomad4 AMR exome

AF:

0.436

Gnomad4 ASJ exome

AF:

0.525

Gnomad4 EAS exome

AF:

0.564

Gnomad4 SAS exome

AF:

0.586

Gnomad4 FIN exome

AF:

0.581

Gnomad4 NFE exome

AF:

0.592

Gnomad4 OTH exome

AF:

0.569

GnomAD4 genome

AF:

0.511

AC:

77537

AN:

151754

Hom.:

20993

Cov.:

AF XY:

0.510

AC XY:

37783

AN XY:

74130

show subpopulations

Gnomad4 AFR

AF:

0.319

Gnomad4 AMR

AF:

0.472

Gnomad4 ASJ

AF:

0.557

Gnomad4 EAS

AF:

0.594

Gnomad4 SAS

AF:

0.595

Gnomad4 FIN

AF:

0.596

Gnomad4 NFE

AF:

0.605

Gnomad4 OTH

AF:

0.536

Alfa

AF:

0.584

Hom.:

22980

Bravo

AF:

0.494

Asia WGS

AF:

0.561

AC:

1951

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

6.7

DANN

Benign

0.84

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