Variant 7-92489923-ATT-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000466.3(PEX1):c.3439-14_3439-13delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0338 in 1,608,206 control chromosomes in the GnomAD database, including 1,057 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 56 hom., cov: 32)

Exomes 𝑓: 0.035 ( 1001 hom. )

Consequence

PEX1
NM_000466.3 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.576

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:

PEX1 (HGNC:):

PEX1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 7-92489923-ATT-A is Benign according to our data. Variant chr7-92489923-ATT-A is described in ClinVar as [Likely_benign]. Clinvar id is 256220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-92489923-ATT-A is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEX1	NM_000466.3 linkuse as main transcript	c.3439-14_3439-13delAA		intron_variant		ENST00000248633.9	NP_000457.1	O43933-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEX1	ENST00000248633.9 linkuse as main transcript	c.3439-14_3439-13delAA		intron_variant		1	NM_000466.3	ENSP00000248633.4		O43933-1

Frequencies

GnomAD3 genomes

AF:

0.0253

AC:

3846

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00705

Gnomad AMI

AF:

0.0471

Gnomad AMR

AF:

0.0216

Gnomad ASJ

AF:

0.0375

Gnomad EAS

AF:

0.00366

Gnomad SAS

AF:

0.0182

Gnomad FIN

AF:

0.0221

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0386

Gnomad OTH

AF:

0.0301

GnomAD3 exomes

AF:

0.0270

AC:

6737

AN:

249814

Hom.:

113

AF XY:

0.0282

AC XY:

3801

AN XY:

135010

show subpopulations

Gnomad AFR exome

AF:

0.00618

Gnomad AMR exome

AF:

0.0147

Gnomad ASJ exome

AF:

0.0425

Gnomad EAS exome

AF:

0.00365

Gnomad SAS exome

AF:

0.0211

Gnomad FIN exome

AF:

0.0235

Gnomad NFE exome

AF:

0.0380

Gnomad OTH exome

AF:

0.0330

GnomAD4 exome

AF:

0.0347

AC:

50466

AN:

1455900

Hom.:

1001

AF XY:

0.0345

AC XY:

25035

AN XY:

724772

show subpopulations

Gnomad4 AFR exome

AF:

0.00626

Gnomad4 AMR exome

AF:

0.0160

Gnomad4 ASJ exome

AF:

0.0402

Gnomad4 EAS exome

AF:

0.00313

Gnomad4 SAS exome

AF:

0.0213

Gnomad4 FIN exome

AF:

0.0221

Gnomad4 NFE exome

AF:

0.0388

Gnomad4 OTH exome

AF:

0.0345

GnomAD4 genome

AF:

0.0252

AC:

3843

AN:

152306

Hom.:

Cov.:

AF XY:

0.0245

AC XY:

1821

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00702

Gnomad4 AMR

AF:

0.0216

Gnomad4 ASJ

AF:

0.0375

Gnomad4 EAS

AF:

0.00367

Gnomad4 SAS

AF:

0.0186

Gnomad4 FIN

AF:

0.0221

Gnomad4 NFE

AF:

0.0385

Gnomad4 OTH

AF:

0.0298

Alfa

AF:

0.0332

Hom.:

Bravo

AF:

0.0258

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Zellweger spectrum disorders

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Apr 11, 2018	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 18, 2023

See Variant Classification Assertion Criteria. -

Peroxisome biogenesis disorder 1A (Zellweger)

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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