dbSNP rs7578605: PXDN:c.3953-14T>C (chr2-1639436-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012293.3(PXDN):c.3953-14T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0641 in 1,613,794 control chromosomes in the GnomAD database, including 3,997 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.087 ( 726 hom., cov: 33)

Exomes 𝑓: 0.062 ( 3271 hom. )

Consequence

PXDN
NM_012293.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.144

Publications

10 publications found

Variant links:

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

PXDN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 2-1639436-A-G is Benign according to our data. Variant chr2-1639436-A-G is described in ClinVar as Benign. ClinVar VariationId is 260229.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 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.3953-14T>C		intron	N/A	NP_036425.1	Q92626-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PXDN	ENST00000252804.9	TSL:1 MANE Select	c.3953-14T>C	intron	N/A	ENSP00000252804.4	Q92626-1
PXDN	ENST00000857505.1		c.3881-14T>C	intron	N/A	ENSP00000527564.1
PXDN	ENST00000453308.1	TSL:3	n.104-14T>C	intron	N/A	ENSP00000414098.1	H7C3W2

Frequencies

GnomAD3 genomes

AF:

0.0874

AC:

13298

AN:

152188

Hom.:

721

Cov.:

show subpopulations

Gnomad AFR

AF:

0.154

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0873

Gnomad ASJ

AF:

0.0421

Gnomad EAS

AF:

0.00789

Gnomad SAS

AF:

0.0159

Gnomad FIN

AF:

0.0503

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0673

Gnomad OTH

AF:

0.0847

GnomAD2 exomes

AF:

0.0608

AC:

15140

AN:

249136

AF XY:

0.0559

show subpopulations

Gnomad AFR exome

AF:

0.158

Gnomad AMR exome

AF:

0.0872

Gnomad ASJ exome

AF:

0.0419

Gnomad EAS exome

AF:

0.00606

Gnomad FIN exome

AF:

0.0497

Gnomad NFE exome

AF:

0.0641

Gnomad OTH exome

AF:

0.0622

GnomAD4 exome

AF:

0.0617

AC:

90166

AN:

1461488

Hom.:

3271

Cov.:

AF XY:

0.0598

AC XY:

43505

AN XY:

727030

show subpopulations

African (AFR)

AF:

0.156

AC:

5204

AN:

33464

American (AMR)

AF:

0.0910

AC:

4069

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.0428

AC:

1119

AN:

26128

East Asian (EAS)

AF:

0.00282

AC:

112

AN:

39700

South Asian (SAS)

AF:

0.0154

AC:

1324

AN:

86250

European-Finnish (FIN)

AF:

0.0520

AC:

2778

AN:

53390

Middle Eastern (MID)

AF:

0.0279

AC:

161

AN:

5762

European-Non Finnish (NFE)

AF:

0.0645

AC:

71742

AN:

1111724

Other (OTH)

AF:

0.0606

AC:

3657

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

4262

8524

12786

17048

21310

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2612

5224

7836

10448

13060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0875

AC:

13326

AN:

152306

Hom.:

726

Cov.:

AF XY:

0.0851

AC XY:

6341

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.154

AC:

6402

AN:

41554

American (AMR)

AF:

0.0875

AC:

1340

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0421

AC:

146

AN:

3472

East Asian (EAS)

AF:

0.00791

AC:

AN:

5184

South Asian (SAS)

AF:

0.0157

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0503

AC:

534

AN:

10614

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0673

AC:

4579

AN:

68024

Other (OTH)

AF:

0.0843

AC:

178

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

623

1246

1869

2492

3115

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

142

284

426

568

710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0722

Hom.:

1877

Bravo

AF:

0.0919

Asia WGS

AF:

0.0290

AC:

103

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Anterior segment dysgenesis 7 (2)

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.39

(source)

DANN

Benign

0.63

PhyloP100

-0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over