rs147066927

Positions:

• chr2-1643470-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012293.3(PXDN):​c.3850G>T​(p.Val1284Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00777 in 1,613,996 control chromosomes in the GnomAD database, including 186 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0061 (10 hom., cov: 31)
  • Exomes 𝑓: 0.0079 (176 hom.)
• Consequence: PXDN NM_012293.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 4.73

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009080559).
• BP6: Variant 2-1643470-C-A is Benign according to our data. Variant chr2-1643470-C-A is described in ClinVar as [Benign]. Clinvar id is 260227.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PXDN	NM_012293.3	c.3850G>T	p.Val1284Leu	missense_variant	19/23	ENST00000252804.9	NP_036425.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PXDN	ENST00000252804.9	c.3850G>T	p.Val1284Leu	missense_variant	19/23	1	NM_012293.3	ENSP00000252804.4
PXDN	ENST00000453308.1	n.1G>T		non_coding_transcript_exon_variant	1/4	3		ENSP00000414098.1
PXDN	ENST00000477093.1	n.492G>T		non_coding_transcript_exon_variant	3/3	4
PXDN	ENST00000478155.5	n.2938G>T		non_coding_transcript_exon_variant	11/15	2

Frequencies

GnomAD3 genomes AF: 0.00609 AC: 927 AN: 152190 Hom.: 10 Cov.: 31

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0116

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0452

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.00542

Gnomad OTH AF: 0.0144

GnomAD3 exomes AF: 0.0114 AC: 2849 AN: 249298 Hom.: 52 AF XY: 0.0136 AC XY: 1837 AN XY: 135246

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.00744

Gnomad ASJ exome AF: 0.0249

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0460

Gnomad FIN exome AF: 0.000511

Gnomad NFE exome AF: 0.00701

Gnomad OTH exome AF: 0.0175

GnomAD4 exome AF: 0.00794 AC: 11611 AN: 1461688 Hom.: 176 Cov.: 34 AF XY: 0.00916 AC XY: 6664 AN XY: 727128

Gnomad4 AFR exome AF: 0.00218

Gnomad4 AMR exome AF: 0.00780

Gnomad4 ASJ exome AF: 0.0245

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0442

Gnomad4 FIN exome AF: 0.000543

Gnomad4 NFE exome AF: 0.00512

Gnomad4 OTH exome AF: 0.0113

GnomAD4 genome AF: 0.00605 AC: 922 AN: 152308 Hom.: 10 Cov.: 31 AF XY: 0.00687 AC XY: 512 AN XY: 74478

Gnomad4 AFR AF: 0.00111

Gnomad4 AMR AF: 0.0116

Gnomad4 ASJ AF: 0.0199

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0452

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00542

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.00722 Hom.: 3

Bravo AF: 0.00569

TwinsUK AF: 0.00431 AC: 16

ALSPAC AF: 0.00701 AC: 27

ESP6500AA AF: 0.00118 AC: 5

ESP6500EA AF: 0.00675 AC: 57

ExAC AF: 0.0118 AC: 1425

Asia WGS AF: 0.0180 AC: 67 AN: 3478

EpiCase AF: 0.00981

EpiControl AF: 0.0119

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Dec 25, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Benign	0.068
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.83	T
MetaRNN	Benign	0.0091	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	1.7	L
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.26
Sift	Benign	0.055	T
Sift4G	Benign	0.078	T
Polyphen		0.24	B
Vest4		0.10
MutPred		0.50		Loss of catalytic residue at F1289 (P = 0.3761);
MPC		0.56
ClinPred		0.016	T
GERP RS		5.3
Varity_R		0.22
gMVP		0.72

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

Other links and lift over

dbSNP: rs147066927; hg19: chr2-1647242; COSMIC: COSV53244501;