Variant 8-51345869-A-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.3980T>A(p.Val1327Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0193 in 1,612,452 control chromosomes in the GnomAD database, including 724 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.041 ( 266 hom., cov: 32)

Exomes 𝑓: 0.017 ( 458 hom. )

Consequence

PXDNL
NM_144651.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.177

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:

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=0.004524559).

BP6

Variant 8-51345869-A-T is Benign according to our data. Variant chr8-51345869-A-T is described in ClinVar as [Benign]. Clinvar id is 3056506.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 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.3980T>A	p.Val1327Asp	missense_variant	20/23	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.3980T>A	p.Val1327Asp	missense_variant	20/23	1	NM_144651.5	ENSP00000348645	P1	A1KZ92-1
PXDNL	ENST00000522933.5 linkuse as main transcript	c.1202T>A	p.Val401Asp	missense_variant	3/6	5		ENSP00000428114
PXDNL	ENST00000522628.5 linkuse as main transcript	c.1700-24972T>A		intron_variant, NMD_transcript_variant		2		ENSP00000429855

Frequencies

GnomAD3 genomes

AF:

0.0408

AC:

6216

AN:

152194

Hom.:

265

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0284

Gnomad ASJ

AF:

0.0268

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0289

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0144

Gnomad OTH

AF:

0.0382

GnomAD3 exomes

AF:

0.0209

AC:

5210

AN:

248980

Hom.:

154

AF XY:

0.0202

AC XY:

2724

AN XY:

135052

show subpopulations

Gnomad AFR exome

AF:

0.110

Gnomad AMR exome

AF:

0.0180

Gnomad ASJ exome

AF:

0.0272

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.0275

Gnomad FIN exome

AF:

0.000882

Gnomad NFE exome

AF:

0.0144

Gnomad OTH exome

AF:

0.0200

GnomAD4 exome

AF:

0.0170

AC:

24876

AN:

1460140

Hom.:

458

Cov.:

AF XY:

0.0173

AC XY:

12536

AN XY:

726482

show subpopulations

Gnomad4 AFR exome

AF:

0.112

Gnomad4 AMR exome

AF:

0.0205

Gnomad4 ASJ exome

AF:

0.0276

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0282

Gnomad4 FIN exome

AF:

0.00107

Gnomad4 NFE exome

AF:

0.0138

Gnomad4 OTH exome

AF:

0.0230

GnomAD4 genome

AF:

0.0409

AC:

6224

AN:

152312

Hom.:

266

Cov.:

AF XY:

0.0396

AC XY:

2948

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.107

Gnomad4 AMR

AF:

0.0284

Gnomad4 ASJ

AF:

0.0268

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0290

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.0144

Gnomad4 OTH

AF:

0.0378

Alfa

AF:

0.0236

Hom.:

Bravo

AF:

0.0457

TwinsUK

AF:

0.0111

AC:

ALSPAC

AF:

0.0106

AC:

ESP6500AA

AF:

0.103

AC:

394

ESP6500EA

AF:

0.0181

AC:

149

ExAC

AF:

0.0219

AC:

2645

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.0176

EpiControl

AF:

0.0183

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

Feb 14, 2020

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

0.042

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.41

CADD

Benign

6.7

DANN

Benign

0.50

DEOGEN2

Benign

0.0017

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.00022

LIST_S2

Benign

0.27

MetaRNN

Benign

0.0045

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.6

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.31

PROVEAN

Benign

1.8

REVEL

Uncertain

0.30

Sift

Benign

0.58

Sift4G

Benign

0.49

Polyphen

0.0

Vest4

0.048

MPC

0.18

ClinPred

0.00030

GERP RS

0.082

Varity_R

0.062

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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