dbSNP rs6473599: PXDNL:p.His376His (chr8-51453640-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_144651.5(PXDNL):c.1128C>T(p.His376His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.911 in 1,613,778 control chromosomes in the GnomAD database, including 676,821 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.82 ( 52908 hom., cov: 32)

Exomes 𝑓: 0.92 ( 623913 hom. )

Consequence

PXDNL
NM_144651.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.79

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 8-51453640-G-A is Benign according to our data. Variant chr8-51453640-G-A is described in ClinVar as [Benign]. Clinvar id is 403357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.79 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PXDNL	NM_144651.5 link	c.1128C>T	p.His376His	synonymous_variant	Exon 10 of 23	ENST00000356297.5	NP_653252.4	A1KZ92-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PXDNL	ENST00000356297.5 link	c.1128C>T	p.His376His	synonymous_variant	Exon 10 of 23	1	NM_144651.5	ENSP00000348645.4		A1KZ92-1

Frequencies

GnomAD3 genomes

AF:

0.816

AC:

124107

AN:

152046

Hom.:

52892

Cov.:

show subpopulations

Gnomad AFR

AF:

0.554

Gnomad AMI

AF:

0.989

Gnomad AMR

AF:

0.891

Gnomad ASJ

AF:

0.907

Gnomad EAS

AF:

0.684

Gnomad SAS

AF:

0.851

Gnomad FIN

AF:

0.919

Gnomad MID

AF:

0.829

Gnomad NFE

AF:

0.943

Gnomad OTH

AF:

0.831

GnomAD3 exomes

AF:

0.881

AC:

219671

AN:

249236

Hom.:

98494

AF XY:

0.886

AC XY:

119722

AN XY:

135194

show subpopulations

Gnomad AFR exome

AF:

0.544

Gnomad AMR exome

AF:

0.930

Gnomad ASJ exome

AF:

0.915

Gnomad EAS exome

AF:

0.689

Gnomad SAS exome

AF:

0.857

Gnomad FIN exome

AF:

0.925

Gnomad NFE exome

AF:

0.938

Gnomad OTH exome

AF:

0.891

GnomAD4 exome

AF:

0.921

AC:

1345508

AN:

1461614

Hom.:

623913

Cov.:

AF XY:

0.920

AC XY:

668901

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.538

Gnomad4 AMR exome

AF:

0.925

Gnomad4 ASJ exome

AF:

0.918

Gnomad4 EAS exome

AF:

0.696

Gnomad4 SAS exome

AF:

0.858

Gnomad4 FIN exome

AF:

0.927

Gnomad4 NFE exome

AF:

0.947

Gnomad4 OTH exome

AF:

0.887

GnomAD4 genome

AF:

0.816

AC:

124164

AN:

152164

Hom.:

52908

Cov.:

AF XY:

0.816

AC XY:

60675

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.553

Gnomad4 AMR

AF:

0.892

Gnomad4 ASJ

AF:

0.907

Gnomad4 EAS

AF:

0.684

Gnomad4 SAS

AF:

0.852

Gnomad4 FIN

AF:

0.919

Gnomad4 NFE

AF:

0.943

Gnomad4 OTH

AF:

0.831

Alfa

AF:

0.883

Hom.:

38487

Bravo

AF:

0.802

Asia WGS

AF:

0.737

AC:

2565

AN:

3478

EpiCase

AF:

0.937

EpiControl

AF:

0.933

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

PXDNL-related disorder

Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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). -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

1.3

DANN

Benign

0.44

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