rs150005994

chr7-92489923-ATT-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000466.3(PEX1):c.3439-14_3439-13del variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.576

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]

(HGNC:):

ACMG classification

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	UniProt
PEX1	NM_000466.3	c.3439-14_3439-13del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000248633.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEX1	ENST00000248633.9	c.3439-14_3439-13del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000466.3	P1
	ENST00000658444.1	n.575-1319_575-1318del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0253 AC: 3846 AN: 152188 Hom.: 57 Cov.: 32

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

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

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.: 56 Cov.: 32 AF XY: 0.0245 AC XY: 1821 AN XY: 74468

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.: 17

Bravo AF: 0.0258

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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	-	- -

Zellweger spectrum disorders Benign:2

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

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

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

Other links and lift over

dbSNP: rs150005994; hg19: chr7-92119237;