Genetic Variant PEX1:c.2584-10delT (chr7-92499847-CA-C) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The NM_000466.3(PEX1):c.2584-10delT variant causes a intron change. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.75 ( 40360 hom., cov: 0)

Exomes 𝑓: 0.59 ( 117822 hom. )

Failed GnomAD Quality Control

Consequence

PEX1
NM_000466.3 intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:12

Conservation

PhyloP100: 5.05

Variant links:

Genes affected

PEX1 (HGNC:8850): (peroxisomal biogenesis factor 1) This gene encodes a member of the AAA ATPase family, a large group of ATPases associated with diverse cellular activities. This protein is cytoplasmic but is often anchored to a peroxisomal membrane where it forms a heteromeric complex and plays a role in the import of proteins into peroxisomes and peroxisome biogenesis. Mutations in this gene have been associated with complementation group 1 peroxisomal disorders such as neonatal adrenoleukodystrophy, infantile Refsum disease, and Zellweger syndrome. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2013]

PEX1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 7-92499847-CA-C is Benign according to our data. Variant chr7-92499847-CA-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 360922.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Benign=6, Uncertain_significance=1}. Variant chr7-92499847-CA-C is described in Lovd as [Benign]. Variant chr7-92499847-CA-C is described in Lovd as [Benign]. Variant chr7-92499847-CA-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX1	NM_000466.3 link	c.2584-10delT		intron_variant	Intron 15 of 23	ENST00000248633.9	NP_000457.1	O43933-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX1	ENST00000248633.9 link	c.2584-10delT		intron_variant	Intron 15 of 23	1	NM_000466.3	ENSP00000248633.4		O43933-1

Frequencies

GnomAD3 genomes

AF:

0.745

AC:

108881

AN:

146078

Hom.:

40356

Cov.:

show subpopulations

Gnomad AFR

AF:

0.625

Gnomad AMI

AF:

0.819

Gnomad AMR

AF:

0.768

Gnomad ASJ

AF:

0.779

Gnomad EAS

AF:

0.689

Gnomad SAS

AF:

0.851

Gnomad FIN

AF:

0.782

Gnomad MID

AF:

0.776

Gnomad NFE

AF:

0.800

Gnomad OTH

AF:

0.753

GnomAD3 exomes

AF:

0.597

AC:

91804

AN:

153898

Hom.:

17289

AF XY:

0.596

AC XY:

48412

AN XY:

81294

show subpopulations

Gnomad AFR exome

AF:

0.538

Gnomad AMR exome

AF:

0.566

Gnomad ASJ exome

AF:

0.563

Gnomad EAS exome

AF:

0.566

Gnomad SAS exome

AF:

0.593

Gnomad FIN exome

AF:

0.626

Gnomad NFE exome

AF:

0.620

Gnomad OTH exome

AF:

0.584

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.585

AC:

683458

AN:

1168006

Hom.:

117822

Cov.:

AF XY:

0.584

AC XY:

342329

AN XY:

586582

show subpopulations

Gnomad4 AFR exome

AF:

0.510

Gnomad4 AMR exome

AF:

0.556

Gnomad4 ASJ exome

AF:

0.559

Gnomad4 EAS exome

AF:

0.547

Gnomad4 SAS exome

AF:

0.568

Gnomad4 FIN exome

AF:

0.583

Gnomad4 NFE exome

AF:

0.593

Gnomad4 OTH exome

AF:

0.576

GnomAD4 genome

AF:

0.745

AC:

108923

AN:

146176

Hom.:

40360

Cov.:

AF XY:

0.746

AC XY:

53145

AN XY:

71248

show subpopulations

Gnomad4 AFR

AF:

0.624

Gnomad4 AMR

AF:

0.768

Gnomad4 ASJ

AF:

0.779

Gnomad4 EAS

AF:

0.689

Gnomad4 SAS

AF:

0.851

Gnomad4 FIN

AF:

0.782

Gnomad4 NFE

AF:

0.800

Gnomad4 OTH

AF:

0.754

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:12

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Benign:5

Nov 23, 2016

Eurofins Ntd Llc (ga)

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely 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: ExAC: 34.4% (31/90) South Asian chromosomes -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aug 26, 2022

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Peroxisome biogenesis disorder 1A (Zellweger)

Uncertain:1Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Zellweger spectrum disorders

Benign:2

May 15, 2017

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Heimler syndrome 1

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Aug 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Peroxisome biogenesis disorder

Benign:1

Jun 15, 2023

Molecular Genetics, Royal Melbourne Hospital

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Peroxisome biogenesis disorder 1B

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

7-92499847-CAAAA-CAAA

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