NM_012293.3:c.1018+9C>T

Variant names:

• chr2-1673634-G-A
• rs182152963
• NM_012293.3:c.1018+9C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_012293.3(PXDN):​c.1018+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00091 in 1,598,472 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (7 hom., cov: 33)
  • Exomes 𝑓: 0.00061 (5 hom.)
• Consequence: PXDN NM_012293.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.307
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• anterior segment dysgenesis 7

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, PanelApp Australia, ClinGen, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 2-1673634-G-A is Benign according to our data. Variant chr2-1673634-G-A is described in ClinVar as Benign. ClinVar VariationId is 471909.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00374 (570/152282) while in subpopulation AFR AF = 0.0128 (533/41536). AF 95% confidence interval is 0.0119. There are 7 homozygotes in GnomAd4. There are 292 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012293.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PXDN	NM_012293.3	MANE Select	c.1018+9C>T		intron	N/A	NP_036425.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PXDN	ENST00000252804.9	TSL:1 MANE Select	c.1018+9C>T		intron	N/A	ENSP00000252804.4
	PXDN	ENST00000433670.5	TSL:1	c.1003+9C>T		intron	N/A	ENSP00000402738.1
	PXDN	ENST00000425171.2	TSL:5	c.946+9C>T		intron	N/A	ENSP00000398363.2

Frequencies

GnomAD3 genomes AF: 0.00370 AC: 563 AN: 152166 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.0127

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

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: 0.0000588

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.00108 AC: 266 AN: 245580 AF XY: 0.000954

Gnomad AFR exome AF: 0.0153

Gnomad AMR exome AF: 0.000207

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000180

Gnomad OTH exome AF: 0.000505

GnomAD4 exome AF: 0.000611 AC: 884 AN: 1446190 Hom.: 5 Cov.: 31 AF XY: 0.000543 AC XY: 389 AN XY: 717040

African (AFR) AF: 0.0167 AC: 554 AN: 33224

American (AMR) AF: 0.000248 AC: 11 AN: 44296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25750

East Asian (EAS) AF: 0.00 AC: 0 AN: 39340

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53142

Middle Eastern (MID) AF: 0.00140 AC: 8 AN: 5700

European-Non Finnish (NFE) AF: 0.000238 AC: 262 AN: 1100496

Other (OTH) AF: 0.000806 AC: 48 AN: 59582

GnomAD4 genome AF: 0.00374 AC: 570 AN: 152282 Hom.: 7 Cov.: 33 AF XY: 0.00392 AC XY: 292 AN XY: 74456

African (AFR) AF: 0.0128 AC: 533 AN: 41536

American (AMR) AF: 0.00163 AC: 25 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68028

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00211 Hom.: 2

Bravo AF: 0.00445

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Anterior segment dysgenesis 7 Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.7
DANN	Benign	0.66
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs182152963; hg19: chr2-1677406;