7-92499847-CAAAA-CAAAAA

Variant names:

• chr7-92499847-C-CA
• rs5885806
• NM_000466.3:c.2584-10dupT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000466.3(PEX1):​c.2584-10dupT variant causes a intron change. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.041 (145 hom., cov: 0)
  • Exomes 𝑓: 0.040 (49 hom.)
• Consequence: PEX1 NM_000466.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 5.05
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• peroxisome biogenesis disorder

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• peroxisome biogenesis disorder 1A (Zellweger)

  Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health, Ambry Genetics
• Heimler syndrome 1

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, G2P, Ambry Genetics
• peroxisome biogenesis disorder 1B

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• Zellweger spectrum disorders

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000244055 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 7-92499847-C-CA is Benign according to our data. Variant chr7-92499847-C-CA is described in ClinVar as Benign. ClinVar VariationId is 286353.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0503 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX1	ENST00000248633.9	c.2584-10_2584-9insT		intron_variant	Intron 15 of 23	1	NM_000466.3	ENSP00000248633.4

Frequencies

GnomAD3 genomes AF: 0.0405 AC: 5911 AN: 146112 Hom.: 146 Cov.: 0

Gnomad AFR AF: 0.0520

Gnomad AMI AF: 0.0124

Gnomad AMR AF: 0.0231

Gnomad ASJ AF: 0.0186

Gnomad EAS AF: 0.0102

Gnomad SAS AF: 0.0262

Gnomad FIN AF: 0.0416

Gnomad MID AF: 0.0292

Gnomad NFE AF: 0.0423

Gnomad OTH AF: 0.0339

GnomAD2 exomes AF: 0.0456 AC: 7020 AN: 153898 AF XY: 0.0468

Gnomad AFR exome AF: 0.0626

Gnomad AMR exome AF: 0.0180

Gnomad ASJ exome AF: 0.0213

Gnomad EAS exome AF: 0.0120

Gnomad FIN exome AF: 0.0488

Gnomad NFE exome AF: 0.0601

Gnomad OTH exome AF: 0.0398

GnomAD4 exome AF: 0.0397 AC: 46580 AN: 1173076 Hom.: 49 Cov.: 0 AF XY: 0.0394 AC XY: 23233 AN XY: 589258

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0515 AC: 1461 AN: 28348

American (AMR) AF: 0.0156 AC: 600 AN: 38584

Ashkenazi Jewish (ASJ) AF: 0.0164 AC: 367 AN: 22356

East Asian (EAS) AF: 0.00667 AC: 235 AN: 35210

South Asian (SAS) AF: 0.0258 AC: 1865 AN: 72152

European-Finnish (FIN) AF: 0.0412 AC: 1845 AN: 44800

Middle Eastern (MID) AF: 0.0249 AC: 124 AN: 4972

European-Non Finnish (NFE) AF: 0.0437 AC: 38312 AN: 877112

Other (OTH) AF: 0.0357 AC: 1771 AN: 49542

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0405 AC: 5923 AN: 146208 Hom.: 145 Cov.: 0 AF XY: 0.0401 AC XY: 2862 AN XY: 71286

African (AFR) AF: 0.0522 AC: 2051 AN: 39308

American (AMR) AF: 0.0231 AC: 340 AN: 14748

Ashkenazi Jewish (ASJ) AF: 0.0186 AC: 63 AN: 3382

East Asian (EAS) AF: 0.0107 AC: 53 AN: 4974

South Asian (SAS) AF: 0.0260 AC: 121 AN: 4660

European-Finnish (FIN) AF: 0.0416 AC: 396 AN: 9512

Middle Eastern (MID) AF: 0.0243 AC: 7 AN: 288

European-Non Finnish (NFE) AF: 0.0423 AC: 2813 AN: 66424

Other (OTH) AF: 0.0336 AC: 68 AN: 2026

Alfa AF: 0.0326 Hom.: 1774

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Zellweger spectrum disorders Benign:2

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:2

Nov 05, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 21, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Feb 25, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.0
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs5885806; hg19: chr7-92129161;