rs161058

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Publications

14 publications found

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 Gene-Disease associations (from GenCC):

peroxisome biogenesis disorder
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
peroxisome biogenesis disorder 10A (Zellweger)
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
peroxisome biogenesis disorder 10B
Inheritance: AR Classification: STRONG Submitted by: G2P
Zellweger spectrum disorders
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PEX3 links:

ENSG00000278206 (HGNC:):

ENSG00000278206 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003630.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX3	NM_003630.3	MANE Select	c.942-13A>G		intron	N/A	NP_003621.1	P56589

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PEX3	ENST00000367591.5	TSL:1 MANE Select	c.942-13A>G	intron	N/A	ENSP00000356563.4	P56589
PEX3	ENST00000918413.1		c.939-13A>G	intron	N/A	ENSP00000588472.1
PEX3	ENST00000951239.1		c.819-13A>G	intron	N/A	ENSP00000621298.1

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

GnomAD2 exomes

AF:

0.447

AC:

112181

AN:

250818

AF XY:

0.430

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 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

African (AFR)

AF:

0.792

AC:

23412

AN:

29550

American (AMR)

AF:

0.602

AC:

26728

AN:

44408

Ashkenazi Jewish (ASJ)

AF:

0.436

AC:

10831

AN:

24818

East Asian (EAS)

AF:

0.614

AC:

23725

AN:

38652

South Asian (SAS)

AF:

0.388

AC:

31920

AN:

82204

European-Finnish (FIN)

AF:

0.445

AC:

23653

AN:

53096

Middle Eastern (MID)

AF:

0.307

AC:

1651

AN:

5382

European-Non Finnish (NFE)

AF:

0.342

AC:

316631

AN:

924936

Other (OTH)

AF:

0.400

AC:

21384

AN:

53498

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

14403

28806

43210

57613

72016

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9760

19520

29280

39040

48800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.504

AC:

76536

AN:

151852

Hom.:

21911

Cov.:

AF XY:

0.508

AC XY:

37717

AN XY:

74210

show subpopulations

African (AFR)

AF:

0.780

AC:

32345

AN:

41454

American (AMR)

AF:

0.539

AC:

8209

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.448

AC:

1550

AN:

3460

East Asian (EAS)

AF:

0.555

AC:

2869

AN:

5174

South Asian (SAS)

AF:

0.396

AC:

1910

AN:

4820

European-Finnish (FIN)

AF:

0.472

AC:

4967

AN:

10528

Middle Eastern (MID)

AF:

0.329

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.344

AC:

23364

AN:

67886

Other (OTH)

AF:

0.468

AC:

987

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1689

3377

5066

6754

8443

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

650

1300

1950

2600

3250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.403

Hom.:

3877

Bravo

AF:

0.525

Asia WGS

AF:

0.492

AC:

1714

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Peroxisome biogenesis disorder 10A (Zellweger) (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Benign

0.77

PhyloP100

-0.048

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over