Variant 8-51320848-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_144651.5(PXDNL):c.4196G>A(p.Arg1399Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,612,848 control chromosomes in the GnomAD database, including 63,624 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1399S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.34 ( 10404 hom., cov: 33)

Exomes 𝑓: 0.26 ( 53220 hom. )

Consequence

PXDNL
NM_144651.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.106

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.408999E-5).

BP6

Variant 8-51320848-C-T is Benign according to our data. Variant chr8-51320848-C-T is described in ClinVar as [Benign]. Clinvar id is 3060925.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PXDNL	NM_144651.5 linkuse as main transcript	c.4196G>A	p.Arg1399Lys	missense_variant	22/23	ENST00000356297.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PXDNL	ENST00000356297.5 linkuse as main transcript	c.4196G>A	p.Arg1399Lys	missense_variant	22/23	1	NM_144651.5	P1	A1KZ92-1
	ENST00000521294.1 linkuse as main transcript	n.249C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.339

AC:

51532

AN:

151942

Hom.:

10384

Cov.:

show subpopulations

Gnomad AFR

AF:

0.565

Gnomad AMI

AF:

0.176

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.283

Gnomad EAS

AF:

0.156

Gnomad SAS

AF:

0.227

Gnomad FIN

AF:

0.231

Gnomad MID

AF:

0.348

Gnomad NFE

AF:

0.266

Gnomad OTH

AF:

0.327

GnomAD3 exomes

AF:

0.261

AC:

64686

AN:

248124

Hom.:

9607

AF XY:

0.257

AC XY:

34597

AN XY:

134684

show subpopulations

Gnomad AFR exome

AF:

0.576

Gnomad AMR exome

AF:

0.219

Gnomad ASJ exome

AF:

0.284

Gnomad EAS exome

AF:

0.152

Gnomad SAS exome

AF:

0.226

Gnomad FIN exome

AF:

0.230

Gnomad NFE exome

AF:

0.261

Gnomad OTH exome

AF:

0.262

GnomAD4 exome

AF:

0.264

AC:

384999

AN:

1460788

Hom.:

53220

Cov.:

AF XY:

0.262

AC XY:

190398

AN XY:

726728

show subpopulations

Gnomad4 AFR exome

AF:

0.577

Gnomad4 AMR exome

AF:

0.222

Gnomad4 ASJ exome

AF:

0.289

Gnomad4 EAS exome

AF:

0.142

Gnomad4 SAS exome

AF:

0.229

Gnomad4 FIN exome

AF:

0.233

Gnomad4 NFE exome

AF:

0.263

Gnomad4 OTH exome

AF:

0.276

GnomAD4 genome

AF:

0.339

AC:

51598

AN:

152060

Hom.:

10404

Cov.:

AF XY:

0.332

AC XY:

24666

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.565

Gnomad4 AMR

AF:

0.250

Gnomad4 ASJ

AF:

0.283

Gnomad4 EAS

AF:

0.155

Gnomad4 SAS

AF:

0.228

Gnomad4 FIN

AF:

0.231

Gnomad4 NFE

AF:

0.266

Gnomad4 OTH

AF:

0.327

Alfa

AF:

0.277

Hom.:

13951

Bravo

AF:

0.350

TwinsUK

AF:

0.277

AC:

1028

ALSPAC

AF:

0.254

AC:

978

ESP6500AA

AF:

0.540

AC:

2105

ESP6500EA

AF:

0.262

AC:

2170

ExAC

AF:

0.270

AC:

32625

Asia WGS

AF:

0.240

AC:

839

AN:

3478

EpiCase

AF:

0.265

EpiControl

AF:

0.261

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PXDNL-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.57

Cadd

Benign

1.2

Dann

Benign

0.63

DEOGEN2

Benign

0.0024

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0026

LIST_S2

Benign

0.078

MetaRNN

Benign

0.000074

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-1.1

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.26

PROVEAN

Benign

0.52

REVEL

Benign

0.050

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.019

MPC

0.11

ClinPred

0.00030

GERP RS

0.65

Varity_R

0.046

gMVP

0.50

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over