rs200996147

Variant names:

• chr2-1666392-C-T
• rs200996147
• NM_012293.3:c.1113G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-1666392-C-T
• chr2-1666392-C-G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_012293.3(PXDN):​c.1113G>A​(p.Pro371Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000788 in 1,612,372 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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (7 hom., cov: 33)
  • Exomes 𝑓: 0.00048 (5 hom.)
• Consequence: PXDN NM_012293.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -6.88
• 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: ClinGen, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.042).
• BP6: Variant 2-1666392-C-T is Benign according to our data. Variant chr2-1666392-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 471910.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-6.88 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00372 (567/152318) while in subpopulation AFR AF = 0.0127 (530/41574). AF 95% confidence interval is 0.0119. There are 7 homozygotes in GnomAd4. There are 291 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PXDN	NM_012293.3	MANE Select	c.1113G>A	p.Pro371Pro	synonymous	Exon 10 of 23	NP_036425.1	Q92626-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PXDN	ENST00000252804.9	TSL:1 MANE Select	c.1113G>A	p.Pro371Pro	synonymous	Exon 10 of 23	ENSP00000252804.4	Q92626-1
	PXDN	ENST00000433670.5	TSL:1	c.1098G>A	p.Pro366Pro	synonymous	Exon 10 of 16	ENSP00000402738.1	H7C1W1
	PXDN	ENST00000857505.1		c.1041G>A	p.Pro347Pro	synonymous	Exon 9 of 22	ENSP00000527564.1

Frequencies

GnomAD3 genomes AF: 0.00368 AC: 560 AN: 152200 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.0126

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: 0.00382

GnomAD2 exomes AF: 0.00105 AC: 256 AN: 242952 AF XY: 0.000913

Gnomad AFR exome AF: 0.0158

Gnomad AMR exome AF: 0.000204

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000646

Gnomad OTH exome AF: 0.000504

GnomAD4 exome AF: 0.000482 AC: 704 AN: 1460054 Hom.: 5 Cov.: 31 AF XY: 0.000431 AC XY: 313 AN XY: 726100

African (AFR) AF: 0.0169 AC: 566 AN: 33440

American (AMR) AF: 0.000247 AC: 11 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000349 AC: 3 AN: 86016

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53252

Middle Eastern (MID) AF: 0.00196 AC: 10 AN: 5092

European-Non Finnish (NFE) AF: 0.0000495 AC: 55 AN: 1111590

Other (OTH) AF: 0.000979 AC: 59 AN: 60242

GnomAD4 genome AF: 0.00372 AC: 567 AN: 152318 Hom.: 7 Cov.: 33 AF XY: 0.00391 AC XY: 291 AN XY: 74468

African (AFR) AF: 0.0127 AC: 530 AN: 41574

American (AMR) AF: 0.00163 AC: 25 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

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

Other (OTH) AF: 0.00378 AC: 8 AN: 2116

Alfa AF: 0.00174 Hom.: 1

Bravo AF: 0.00440

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Anterior segment dysgenesis 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.12
DANN	Benign	0.66
PhyloP100		-6.9
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs200996147; hg19: chr2-1670164; COSMIC: COSV53236927;