Variant 8-51339745-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_144651.5(PXDNL):c.4025A>C(p.Asp1342Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 1,595,844 control chromosomes in the GnomAD database, including 27 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 (★★).

Frequency

Genomes: 𝑓 0.0082 ( 12 hom., cov: 33)

Exomes 𝑓: 0.00077 ( 15 hom. )

Consequence

PXDNL
NM_144651.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.326

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028561056).

BP6

Variant 8-51339745-T-G is Benign according to our data. Variant chr8-51339745-T-G is described in ClinVar as [Benign]. Clinvar id is 792106.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00818 (1246/152358) while in subpopulation AFR AF= 0.0285 (1184/41576). AF 95% confidence interval is 0.0271. There are 12 homozygotes in gnomad4. There are 596 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PXDNL	NM_144651.5 link	c.4025A>C	p.Asp1342Ala	missense_variant	21/23	ENST00000356297.5	NP_653252.4	A1KZ92-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PXDNL	ENST00000356297.5 link	c.4025A>C	p.Asp1342Ala	missense_variant	21/23	1	NM_144651.5	ENSP00000348645.4	A1KZ92-1
PXDNL	ENST00000522933.5 link	c.1244A>C	p.Asp415Ala	missense_variant	4/6	5		ENSP00000428114.1	H0YAV0
PXDNL	ENST00000519183.1 link	n.441A>C		non_coding_transcript_exon_variant	1/3	3
PXDNL	ENST00000522628.5 link	n.1700-18848A>C		intron_variant		2		ENSP00000429855.1	K4DIA6

Frequencies

GnomAD3 genomes

AF:

0.00820

AC:

1248

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0286

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00213

AC:

492

AN:

230796

Hom.:

AF XY:

0.00159

AC XY:

199

AN XY:

125014

show subpopulations

Gnomad AFR exome

AF:

0.0286

Gnomad AMR exome

AF:

0.00168

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000387

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000371

Gnomad OTH exome

AF:

0.000896

GnomAD4 exome

AF:

0.000774

AC:

1117

AN:

1443486

Hom.:

Cov.:

AF XY:

0.000691

AC XY:

495

AN XY:

716848

show subpopulations

Gnomad4 AFR exome

AF:

0.0261

Gnomad4 AMR exome

AF:

0.00184

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000243

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000651

Gnomad4 OTH exome

AF:

0.00191

GnomAD4 genome

AF:

0.00818

AC:

1246

AN:

152358

Hom.:

Cov.:

AF XY:

0.00800

AC XY:

596

AN XY:

74522

show subpopulations

Gnomad4 AFR

AF:

0.0285

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00149

Hom.:

Bravo

AF:

0.00909

ESP6500AA

AF:

0.0257

AC:

ESP6500EA

AF:

0.000123

AC:

ExAC

AF:

0.00224

AC:

270

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000595

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

PXDNL-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 06, 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

0.14

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.20

DEOGEN2

Benign

0.0048

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.071

LIST_S2

Benign

0.36

MetaRNN

Benign

0.0029

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.3

REVEL

Benign

0.031

Sift

Benign

0.55

Sift4G

Benign

0.73

Polyphen

0.0010

Vest4

0.26

MVP

0.30

MPC

0.14

ClinPred

0.0013

GERP RS

2.5

Varity_R

0.035

gMVP

0.078

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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