7-92499847-CAAA-CAA

Position:

• chr7-92499847-CAAA-CAA

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

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
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:12
• Conservation: PhyloP100: 5.05

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 (HGNC:):

ACMG classification

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, Uncertain_significance=1, Benign=6}. 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/exons	MANE	Protein	UniProt
PEX1	NM_000466.3	c.2584-10delT		intron_variant		ENST00000248633.9	NP_000457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEX1	ENST00000248633.9	c.2584-10delT		intron_variant		1	NM_000466.3	ENSP00000248633.4

Frequencies

GnomAD3 genomes AF: 0.745 AC: 108881 AN: 146078 Hom.: 40356 Cov.: 0

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

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.: 0 AF XY: 0.584 AC XY: 342329 AN XY: 586582

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.: 0 AF XY: 0.746 AC XY: 53145 AN XY: 71248

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:1 Benign:12

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Benign:5

Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 23, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	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 -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 26, 2022	- -

Peroxisome biogenesis disorder 1A (Zellweger) Uncertain:1 Benign:1

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Zellweger spectrum disorders Benign:2

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	May 15, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Heimler syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Peroxisome biogenesis disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics, Royal Melbourne Hospital

Jun 15, 2023

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 2019

- -

Peroxisome biogenesis disorder 1B Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs5885806; hg19: chr7-92129161;