Variant 8-51319927-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PXDNL	NM_144651.5 linkuse as main transcript	c.4356C>A	p.Asp1452Glu	missense_variant	23/23	ENST00000356297.5	NP_653252.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PXDNL	ENST00000356297.5 linkuse as main transcript	c.4356C>A	p.Asp1452Glu	missense_variant	23/23	1	NM_144651.5	ENSP00000348645	P1	A1KZ92-1
	ENST00000521294.1 linkuse as main transcript	n.121-793G>T		intron_variant, non_coding_transcript_variant		2

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

GnomAD3 exomes

AF:

0.254

AC:

54271

AN:

213490

Hom.:

8012

AF XY:

0.250

AC XY:

29320

AN XY:

117058

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 SAS exome

AF:

0.220

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

Gnomad4 AFR exome

AF:

0.583

Gnomad4 AMR exome

AF:

0.190

Gnomad4 ASJ exome

AF:

0.285

Gnomad4 EAS exome

AF:

0.121

Gnomad4 SAS exome

AF:

0.223

Gnomad4 FIN exome

AF:

0.231

Gnomad4 NFE exome

AF:

0.262

Gnomad4 OTH exome

AF:

0.273

GnomAD4 genome

AF:

0.339

AC:

51555

AN:

151980

Hom.:

10518

Cov.:

AF XY:

0.332

AC XY:

24636

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.573

Gnomad4 AMR

AF:

0.237

Gnomad4 ASJ

AF:

0.283

Gnomad4 EAS

AF:

0.129

Gnomad4 SAS

AF:

0.226

Gnomad4 FIN

AF:

0.232

Gnomad4 NFE

AF:

0.266

Gnomad4 OTH

AF:

0.331

Alfa

AF:

0.279

Hom.:

10691

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

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PXDNL-related disorder

Benign:1

Benign, no assertion criteria provided

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

0.16

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.71

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

MutationTaster

Benign

1.0

P;P

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

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