rs3762000

Positions:

• chr6-143470941-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003630.3(PEX3):​c.332-20C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 1,599,828 control chromosomes in the GnomAD database, including 51,960 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8652 hom., cov: 32)
  • Exomes 𝑓: 0.24 (43308 hom.)
• Consequence: PEX3 NM_003630.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.143

Genes affected

PEX3 (HGNC:8858): (peroxisomal biogenesis factor 3) The product of this gene is involved in peroxisome biosynthesis and integrity. It assembles membrane vesicles before the matrix proteins are translocated. Peroxins (PEXs) are proteins that are essential for the assembly of functional peroxisomes. The peroxisome biogenesis disorders (PBDs) are a group of genetically heterogeneous autosomal recessive, lethal diseases characterized by multiple defects in peroxisome function. The peroxisomal biogenesis disorders are a heterogeneous group with at least 14 complementation groups and with more than 1 phenotype being observed in cases falling into particular complementation groups. Although the clinical features of PBD patients vary, cells from all PBD patients exhibit a defect in the import of one or more classes of peroxisomal matrix proteins into the organelle. Defects in this gene are a cause Zellweger syndrome (ZWS). [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 6-143470941-C-G is Benign according to our data. Variant chr6-143470941-C-G is described in ClinVar as [Benign]. Clinvar id is 167458.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEX3	NM_003630.3	c.332-20C>G		intron_variant		ENST00000367591.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEX3	ENST00000367591.5	c.332-20C>G		intron_variant		1	NM_003630.3	P1
PEX3	ENST00000367592.5	c.200-20C>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47937 AN: 151880 Hom.: 8620 Cov.: 32

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.282

GnomAD3 exomes AF: 0.269 AC: 67245 AN: 249884 Hom.: 9781 AF XY: 0.263 AC XY: 35590 AN XY: 135156

Gnomad AFR exome AF: 0.499

Gnomad AMR exome AF: 0.277

Gnomad ASJ exome AF: 0.335

Gnomad EAS exome AF: 0.220

Gnomad SAS exome AF: 0.253

Gnomad FIN exome AF: 0.352

Gnomad NFE exome AF: 0.226

Gnomad OTH exome AF: 0.243

GnomAD4 exome AF: 0.237 AC: 343126 AN: 1447830 Hom.: 43308 Cov.: 29 AF XY: 0.237 AC XY: 171067 AN XY: 721102

Gnomad4 AFR exome AF: 0.511

Gnomad4 AMR exome AF: 0.275

Gnomad4 ASJ exome AF: 0.337

Gnomad4 EAS exome AF: 0.262

Gnomad4 SAS exome AF: 0.252

Gnomad4 FIN exome AF: 0.344

Gnomad4 NFE exome AF: 0.217

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.316 AC: 48016 AN: 151998 Hom.: 8652 Cov.: 32 AF XY: 0.318 AC XY: 23641 AN XY: 74290

Gnomad4 AFR AF: 0.495

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.366

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.285

Alfa AF: 0.281 Hom.: 1249

Bravo AF: 0.316

Asia WGS AF: 0.257 AC: 896 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 21, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 11, 2018	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 19, 2014	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.64
DANN	Benign	0.54

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: rs3762000; hg19: chr6-143792078; COSMIC: COSV62567907;