rs6730800

Variant names:

• chr2-1643399-T-C
• rs6730800
• NM_012293.3:c.3921A>G
• PXDN p.Val1307Val

Your query was ambiguous. Multiple possible variants found:

• chr2-1643399-T-C
• chr2-1643399-T-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_012293.3(PXDN):​c.3921A>G​(p.Val1307Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.896 in 1,613,732 control chromosomes in the GnomAD database, including 648,234 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.87 (58332 hom., cov: 33)
  • Exomes 𝑓: 0.90 (589902 hom.)
• Consequence: PXDN NM_012293.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.519
• Publications: 21 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, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 2-1643399-T-C is Benign according to our data. Variant chr2-1643399-T-C is described in ClinVar as Benign. ClinVar VariationId is 260228.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.519 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 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.3921A>G	p.Val1307Val	synonymous	Exon 19 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.3921A>G	p.Val1307Val	synonymous	Exon 19 of 23	ENSP00000252804.4	Q92626-1
	PXDN	ENST00000857505.1		c.3849A>G	p.Val1283Val	synonymous	Exon 18 of 22	ENSP00000527564.1
	PXDN	ENST00000453308.1	TSL:3	n.72A>G		non_coding_transcript_exon	Exon 1 of 4	ENSP00000414098.1	H7C3W2

Frequencies

GnomAD3 genomes AF: 0.874 AC: 132849 AN: 152082 Hom.: 58289 Cov.: 33

Gnomad AFR AF: 0.792

Gnomad AMI AF: 0.914

Gnomad AMR AF: 0.929

Gnomad ASJ AF: 0.901

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.974

Gnomad FIN AF: 0.889

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.889

Gnomad OTH AF: 0.877

GnomAD2 exomes AF: 0.913 AC: 227130 AN: 248898 AF XY: 0.915

Gnomad AFR exome AF: 0.790

Gnomad AMR exome AF: 0.953

Gnomad ASJ exome AF: 0.895

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.887

Gnomad NFE exome AF: 0.893

Gnomad OTH exome AF: 0.912

GnomAD4 exome AF: 0.898 AC: 1312187 AN: 1461532 Hom.: 589902 Cov.: 67 AF XY: 0.900 AC XY: 654521 AN XY: 727056

African (AFR) AF: 0.791 AC: 26482 AN: 33476

American (AMR) AF: 0.951 AC: 42517 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.895 AC: 23385 AN: 26136

East Asian (EAS) AF: 1.00 AC: 39694 AN: 39700

South Asian (SAS) AF: 0.971 AC: 83730 AN: 86256

European-Finnish (FIN) AF: 0.883 AC: 47013 AN: 53252

Middle Eastern (MID) AF: 0.951 AC: 5484 AN: 5766

European-Non Finnish (NFE) AF: 0.890 AC: 989372 AN: 1111852

Other (OTH) AF: 0.903 AC: 54510 AN: 60370

GnomAD4 genome AF: 0.874 AC: 132949 AN: 152200 Hom.: 58332 Cov.: 33 AF XY: 0.878 AC XY: 65304 AN XY: 74392

African (AFR) AF: 0.792 AC: 32869 AN: 41514

American (AMR) AF: 0.929 AC: 14217 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.901 AC: 3129 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5158 AN: 5164

South Asian (SAS) AF: 0.974 AC: 4691 AN: 4816

European-Finnish (FIN) AF: 0.889 AC: 9421 AN: 10600

Middle Eastern (MID) AF: 0.956 AC: 281 AN: 294

European-Non Finnish (NFE) AF: 0.889 AC: 60493 AN: 68018

Other (OTH) AF: 0.879 AC: 1856 AN: 2112

Alfa AF: 0.887 Hom.: 93945

Bravo AF: 0.872

Asia WGS AF: 0.977 AC: 3395 AN: 3478

EpiCase AF: 0.896

EpiControl AF: 0.898

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.7
DANN	Benign	0.48
PhyloP100		0.52
Mutation Taster		=98/2	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6730800;

hg19: chr2-1647171;

COSMIC: COSV108052324;