NM_012293.3:c.2661C>T

Variant names:

• chr2-1649119-G-A
• rs1863134
• NM_012293.3:c.2661C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_012293.3(PXDN):​c.2661C>T​(p.Ser887Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00865 in 1,612,636 control chromosomes in the GnomAD database, including 905 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.044 (463 hom., cov: 32)
  • Exomes 𝑓: 0.0050 (442 hom.)
• Consequence: PXDN NM_012293.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0520
• Publications: 2 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 (BayesDel_noAF=-0.41).
• BP6: Variant 2-1649119-G-A is Benign according to our data. Variant chr2-1649119-G-A is described in ClinVar as Benign. ClinVar VariationId is 260222.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.052 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

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.2661C>T	p.Ser887Ser	synonymous	Exon 17 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.2661C>T	p.Ser887Ser	synonymous	Exon 17 of 23	ENSP00000252804.4	Q92626-1
	PXDN	ENST00000857505.1		c.2589C>T	p.Ser863Ser	synonymous	Exon 16 of 22	ENSP00000527564.1
	PXDN	ENST00000478155.5	TSL:2	n.2697-4367C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0439 AC: 6674 AN: 151986 Hom.: 462 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0170

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00814

Gnomad SAS AF: 0.00601

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.0450

GnomAD2 exomes AF: 0.0120 AC: 2947 AN: 245288 AF XY: 0.00968

Gnomad AFR exome AF: 0.160

Gnomad AMR exome AF: 0.00747

Gnomad ASJ exome AF: 0.000503

Gnomad EAS exome AF: 0.00598

Gnomad FIN exome AF: 0.0000466

Gnomad NFE exome AF: 0.000408

Gnomad OTH exome AF: 0.00752

GnomAD4 exome AF: 0.00496 AC: 7251 AN: 1460532 Hom.: 442 Cov.: 86 AF XY: 0.00444 AC XY: 3227 AN XY: 726552

African (AFR) AF: 0.158 AC: 5287 AN: 33476

American (AMR) AF: 0.00868 AC: 388 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26114

East Asian (EAS) AF: 0.00237 AC: 94 AN: 39700

South Asian (SAS) AF: 0.00424 AC: 366 AN: 86236

European-Finnish (FIN) AF: 0.0000382 AC: 2 AN: 52342

Middle Eastern (MID) AF: 0.00780 AC: 45 AN: 5766

European-Non Finnish (NFE) AF: 0.000360 AC: 400 AN: 1111832

Other (OTH) AF: 0.0110 AC: 665 AN: 60362

GnomAD4 genome AF: 0.0440 AC: 6695 AN: 152104 Hom.: 463 Cov.: 32 AF XY: 0.0427 AC XY: 3176 AN XY: 74346

African (AFR) AF: 0.150 AC: 6227 AN: 41468

American (AMR) AF: 0.0169 AC: 259 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3464

East Asian (EAS) AF: 0.00816 AC: 42 AN: 5150

South Asian (SAS) AF: 0.00602 AC: 29 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000529 AC: 36 AN: 68008

Other (OTH) AF: 0.0450 AC: 95 AN: 2110

Alfa AF: 0.0195 Hom.: 126

Bravo AF: 0.0497

Asia WGS AF: 0.0180 AC: 63 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000711

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	8.6
DANN	Benign	0.80
PhyloP100		-0.052
Mutation Taster		=81/19	polymorphism (auto)

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: rs1863134; hg19: chr2-1652891;