6-143485139-A-G

Position:

chr6-143485139-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003630.3(PEX3):c.942-13A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 1,408,396 control chromosomes in the GnomAD database, including 120,331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 21911 hom., cov: 32)

Exomes 𝑓: 0.38 ( 98420 hom. )

Consequence

PEX3
NM_003630.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.0480

Variant links:

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]

PEX3 links:

PEX3 (HGNC:):

PEX3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 6-143485139-A-G is Benign according to our data. Variant chr6-143485139-A-G is described in ClinVar as [Benign]. Clinvar id is 259108.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEX3	NM_003630.3 linkuse as main transcript	c.942-13A>G		intron_variant		ENST00000367591.5	NP_003621.1	P56589

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PEX3	ENST00000367591.5 linkuse as main transcript	c.942-13A>G	intron_variant		1	NM_003630.3	ENSP00000356563.4	P56589
PEX3	ENST00000585848.1 linkuse as main transcript	n.68A>G	non_coding_transcript_exon_variant	1/2	2
ENSG00000278206	ENST00000591892.2 linkuse as main transcript	n.161A>G	non_coding_transcript_exon_variant	1/5	5

Frequencies

GnomAD3 genomes

AF:

0.504

AC:

76408

AN:

151734

Hom.:

21848

Cov.:

show subpopulations

Gnomad AFR

AF:

0.780

Gnomad AMI

AF:

0.263

Gnomad AMR

AF:

0.539

Gnomad ASJ

AF:

0.448

Gnomad EAS

AF:

0.554

Gnomad SAS

AF:

0.397

Gnomad FIN

AF:

0.472

Gnomad MID

AF:

0.334

Gnomad NFE

AF:

0.344

Gnomad OTH

AF:

0.465

GnomAD3 exomes

AF:

0.447

AC:

112181

AN:

250818

Hom.:

27535

AF XY:

0.430

AC XY:

58332

AN XY:

135586

show subpopulations

Gnomad AFR exome

AF:

0.785

Gnomad AMR exome

AF:

0.610

Gnomad ASJ exome

AF:

0.436

Gnomad EAS exome

AF:

0.550

Gnomad SAS exome

AF:

0.397

Gnomad FIN exome

AF:

0.456

Gnomad NFE exome

AF:

0.348

Gnomad OTH exome

AF:

0.402

GnomAD4 exome

AF:

0.382

AC:

479935

AN:

1256544

Hom.:

98420

Cov.:

AF XY:

0.379

AC XY:

241285

AN XY:

636474

show subpopulations

Gnomad4 AFR exome

AF:

0.792

Gnomad4 AMR exome

AF:

0.602

Gnomad4 ASJ exome

AF:

0.436

Gnomad4 EAS exome

AF:

0.614

Gnomad4 SAS exome

AF:

0.388

Gnomad4 FIN exome

AF:

0.445

Gnomad4 NFE exome

AF:

0.342

Gnomad4 OTH exome

AF:

0.400

GnomAD4 genome

AF:

0.504

AC:

76536

AN:

151852

Hom.:

21911

Cov.:

AF XY:

0.508

AC XY:

37717

AN XY:

74210

show subpopulations

Gnomad4 AFR

AF:

0.780

Gnomad4 AMR

AF:

0.539

Gnomad4 ASJ

AF:

0.448

Gnomad4 EAS

AF:

0.555

Gnomad4 SAS

AF:

0.396

Gnomad4 FIN

AF:

0.472

Gnomad4 NFE

AF:

0.344

Gnomad4 OTH

AF:

0.468

Alfa

AF:

0.403

Hom.:

3877

Bravo

AF:

0.525

Asia WGS

AF:

0.492

AC:

1714

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 13, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 27, 2015	- -

Peroxisome biogenesis disorder 10A (Zellweger)

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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