rs191647762

chr2-1664986-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_012293.3(PXDN):c.1380G>A(p.Pro460=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000809 in 1,565,818 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (7 hom., cov: 33)
  • Exomes 𝑓: 0.00049 (6 hom.)
• Consequence: PXDN NM_012293.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.86

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 2-1664986-C-T is Benign according to our data. Variant chr2-1664986-C-T is described in ClinVar as [Benign]. Clinvar id is 471912.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00385 (579/150284) while in subpopulation AFR AF= 0.0132 (543/41118). AF 95% confidence interval is 0.0123. There are 7 homozygotes in gnomad4. There are 303 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PXDN	NM_012293.3	c.1380G>A	p.Pro460=	synonymous_variant	11/23	ENST00000252804.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PXDN	ENST00000252804.9	c.1380G>A	p.Pro460=	synonymous_variant	11/23	1	NM_012293.3	P1

Frequencies

GnomAD3 genomes AF: 0.00381 AC: 572 AN: 150130 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.0131

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00167

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000443

Gnomad OTH AF: 0.00384

GnomAD3 exomes AF: 0.000991 AC: 244 AN: 246318 Hom.: 0 AF XY: 0.000845 AC XY: 113 AN XY: 133662

Gnomad AFR exome AF: 0.0150

Gnomad AMR exome AF: 0.000204

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000716

Gnomad OTH exome AF: 0.000501

GnomAD4 exome AF: 0.000485 AC: 687 AN: 1415534 Hom.: 6 Cov.: 31 AF XY: 0.000433 AC XY: 305 AN XY: 704826

Gnomad4 AFR exome AF: 0.0180

Gnomad4 AMR exome AF: 0.000255

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000304

Gnomad4 OTH exome AF: 0.00103

GnomAD4 genome AF: 0.00385 AC: 579 AN: 150284 Hom.: 7 Cov.: 33 AF XY: 0.00412 AC XY: 303 AN XY: 73480

Gnomad4 AFR AF: 0.0132

Gnomad4 AMR AF: 0.00166

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000443

Gnomad4 OTH AF: 0.00380

Alfa AF: 0.00198 Hom.: 1

Bravo AF: 0.00449

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.0000595

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Anterior segment dysgenesis 7 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 04, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	0.080
Dann	Benign	0.73

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: rs191647762; hg19: chr2-1668758; COSMIC: COSV53227121; COSMIC: COSV53227121;