rs7560004

Variant names:

• chr2-1674962-G-A
• rs7560004
• NM_012293.3:c.849-1150C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-1674962-G-A
• chr2-1674962-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012293.3(PXDN):​c.849-1150C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,082 control chromosomes in the GnomAD database, including 3,952 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (3952 hom., cov: 32)
• Consequence: PXDN NM_012293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.34 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PXDN	NM_012293.3	MANE Select	c.849-1150C>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.849-1150C>T		intron	N/A	ENSP00000252804.4
	PXDN	ENST00000433670.5	TSL:1	c.834-1150C>T		intron	N/A	ENSP00000402738.1
	PXDN	ENST00000425171.2	TSL:5	c.777-1150C>T		intron	N/A	ENSP00000398363.2

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31119 AN: 151964 Hom.: 3941 Cov.: 32

Gnomad AFR AF: 0.0737

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.192

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.205 AC: 31143 AN: 152082 Hom.: 3952 Cov.: 32 AF XY: 0.214 AC XY: 15915 AN XY: 74306

African (AFR) AF: 0.0735 AC: 3051 AN: 41528

American (AMR) AF: 0.348 AC: 5308 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 519 AN: 3470

East Asian (EAS) AF: 0.309 AC: 1587 AN: 5144

South Asian (SAS) AF: 0.350 AC: 1689 AN: 4820

European-Finnish (FIN) AF: 0.272 AC: 2873 AN: 10566

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15589 AN: 67974

Other (OTH) AF: 0.191 AC: 403 AN: 2108

Alfa AF: 0.227 Hom.: 2224

Bravo AF: 0.201

Asia WGS AF: 0.275 AC: 958 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.39
DANN	Benign	0.60
PhyloP100		-1.6
Mutation Taster		=100/0	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: rs7560004; hg19: chr2-1678734;