Genetic Variant NM_144651.5:c.4356C>A (chr8-51319927-G-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_144651.5(PXDNL):c.4356C>A(p.Asp1452Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 1,555,250 control chromosomes in the GnomAD database, including 60,980 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.34 ( 10518 hom., cov: 32)

Exomes 𝑓: 0.26 ( 50462 hom. )

Consequence

PXDNL
NM_144651.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.00500

Publications

22 publications found

Variant links:

Genes affected

PXDNL (HGNC:26359): (peroxidasin like) Predicted to enable heme binding activity and peroxidase activity. Predicted to be involved in hydrogen peroxide catabolic process. Predicted to be located in cytoplasm. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

PXDNL links:

ENSG00000253664 (HGNC:):

ENSG00000253664 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.5740903E-5).

BP6

Variant 8-51319927-G-T is Benign according to our data. Variant chr8-51319927-G-T is described in ClinVar as Benign. ClinVar VariationId is 3060502.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144651.5. 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
	PXDNL	NM_144651.5	MANE Select	c.4356C>A	p.Asp1452Glu	missense	Exon 23 of 23	NP_653252.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PXDNL	ENST00000356297.5	TSL:1 MANE Select	c.4356C>A	p.Asp1452Glu	missense	Exon 23 of 23	ENSP00000348645.4	A1KZ92-1
PXDNL	ENST00000894552.1		c.4536C>A	p.Asp1512Glu	missense	Exon 24 of 24	ENSP00000564611.1
PXDNL	ENST00000894549.1		c.4284C>A	p.Asp1428Glu	missense	Exon 22 of 22	ENSP00000564608.1

Frequencies

GnomAD3 genomes

AF:

0.339

AC:

51471

AN:

151862

Hom.:

10489

Cov.:

show subpopulations

Gnomad AFR

AF:

0.573

Gnomad AMI

AF:

0.176

Gnomad AMR

AF:

0.237

Gnomad ASJ

AF:

0.283

Gnomad EAS

AF:

0.129

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.232

Gnomad MID

AF:

0.348

Gnomad NFE

AF:

0.266

Gnomad OTH

AF:

0.331

GnomAD2 exomes

AF:

0.254

AC:

54271

AN:

213490

AF XY:

0.250

show subpopulations

Gnomad AFR exome

AF:

0.579

Gnomad AMR exome

AF:

0.185

Gnomad ASJ exome

AF:

0.279

Gnomad EAS exome

AF:

0.118

Gnomad FIN exome

AF:

0.230

Gnomad NFE exome

AF:

0.258

Gnomad OTH exome

AF:

0.257

GnomAD4 exome

AF:

0.261

AC:

366154

AN:

1403270

Hom.:

50462

Cov.:

AF XY:

0.259

AC XY:

180855

AN XY:

697108

show subpopulations

African (AFR)

AF:

0.583

AC:

17863

AN:

30632

American (AMR)

AF:

0.190

AC:

6526

AN:

34416

Ashkenazi Jewish (ASJ)

AF:

0.285

AC:

6894

AN:

24192

East Asian (EAS)

AF:

0.121

AC:

4511

AN:

37240

South Asian (SAS)

AF:

0.223

AC:

17075

AN:

76422

European-Finnish (FIN)

AF:

0.231

AC:

12008

AN:

51898

Middle Eastern (MID)

AF:

0.285

AC:

1573

AN:

5524

European-Non Finnish (NFE)

AF:

0.262

AC:

283953

AN:

1085354

Other (OTH)

AF:

0.273

AC:

15751

AN:

57592

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

12515

25030

37544

50059

62574

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9866

19732

29598

39464

49330

<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:

0.339

AC:

51555

AN:

151980

Hom.:

10518

Cov.:

AF XY:

0.332

AC XY:

24636

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.573

AC:

23740

AN:

41408

American (AMR)

AF:

0.237

AC:

3611

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.283

AC:

983

AN:

3470

East Asian (EAS)

AF:

0.129

AC:

666

AN:

5160

South Asian (SAS)

AF:

0.226

AC:

1089

AN:

4824

European-Finnish (FIN)

AF:

0.232

AC:

2455

AN:

10574

Middle Eastern (MID)

AF:

0.344

AC:

101

AN:

294

European-Non Finnish (NFE)

AF:

0.266

AC:

18053

AN:

67966

Other (OTH)

AF:

0.331

AC:

697

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1571

3143

4714

6286

7857

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

472

944

1416

1888

2360

<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:

0.291

Hom.:

17089

Bravo

AF:

0.348

TwinsUK

AF:

0.276

AC:

1022

ALSPAC

AF:

0.253

AC:

976

ESP6500AA

AF:

0.553

AC:

2093

ESP6500EA

AF:

0.262

AC:

2148

ExAC

AF:

0.265

AC:

31965

Asia WGS

AF:

0.238

AC:

831

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

PXDNL-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.71

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.0020

Eigen

Benign

-0.92

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.32

MetaRNN

Benign

0.000016

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.37

PhyloP100

-0.0050

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.080

REVEL

Benign

0.022

Sift

Benign

0.40

Sift4G

Benign

0.71

Polyphen

0.0080

Vest4

0.042

MutPred

0.075

Gain of glycosylation at P1456 (P = 0.1796)

MPC

0.11

ClinPred

0.00030

GERP RS

-0.13

Varity_R

0.042

gMVP

0.42

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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