6-143471538-T-C

Variant names:

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.524-19T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 1,598,930 control chromosomes in the GnomAD database, including 125,878 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10569 hom., cov: 32)

Exomes 𝑓: 0.40 ( 115309 hom. )

Consequence

PEX3
NM_003630.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.831

Publications

9 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:

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=-0.81).

BP6

Variant 6-143471538-T-C is Benign according to our data. Variant chr6-143471538-T-C is described in ClinVar as Benign. ClinVar VariationId is 259107.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.446 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.524-19T>C		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.524-19T>C	intron	N/A	ENSP00000356563.4	P56589
PEX3	ENST00000918413.1		c.521-19T>C	intron	N/A	ENSP00000588472.1
PEX3	ENST00000951239.1		c.524-19T>C	intron	N/A	ENSP00000621298.1

Frequencies

GnomAD3 genomes

AF:

0.366

AC:

55650

AN:

151862

Hom.:

10562

Cov.:

show subpopulations

Gnomad AFR

AF:

0.269

Gnomad AMI

AF:

0.555

Gnomad AMR

AF:

0.455

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.337

Gnomad SAS

AF:

0.252

Gnomad FIN

AF:

0.338

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.419

Gnomad OTH

AF:

0.393

GnomAD2 exomes

AF:

0.379

AC:

94969

AN:

250842

AF XY:

0.373

show subpopulations

Gnomad AFR exome

AF:

0.264

Gnomad AMR exome

AF:

0.458

Gnomad ASJ exome

AF:

0.358

Gnomad EAS exome

AF:

0.331

Gnomad FIN exome

AF:

0.343

Gnomad NFE exome

AF:

0.418

Gnomad OTH exome

AF:

0.397

GnomAD4 exome

AF:

0.395

AC:

571886

AN:

1446952

Hom.:

115309

Cov.:

AF XY:

0.392

AC XY:

282395

AN XY:

720704

show subpopulations

African (AFR)

AF:

0.259

AC:

8603

AN:

33196

American (AMR)

AF:

0.458

AC:

20456

AN:

44668

Ashkenazi Jewish (ASJ)

AF:

0.359

AC:

9322

AN:

26000

East Asian (EAS)

AF:

0.350

AC:

13828

AN:

39520

South Asian (SAS)

AF:

0.254

AC:

21822

AN:

85748

European-Finnish (FIN)

AF:

0.352

AC:

18768

AN:

53320

Middle Eastern (MID)

AF:

0.411

AC:

2323

AN:

5646

European-Non Finnish (NFE)

AF:

0.413

AC:

454111

AN:

1099018

Other (OTH)

AF:

0.379

AC:

22653

AN:

59836

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

15574

31147

46721

62294

77868

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13706

27412

41118

54824

68530

<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:

0.366

AC:

55672

AN:

151978

Hom.:

10569

Cov.:

AF XY:

0.364

AC XY:

27019

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.268

AC:

11120

AN:

41466

American (AMR)

AF:

0.455

AC:

6953

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.347

AC:

1204

AN:

3470

East Asian (EAS)

AF:

0.338

AC:

1748

AN:

5172

South Asian (SAS)

AF:

0.253

AC:

1218

AN:

4818

European-Finnish (FIN)

AF:

0.338

AC:

3564

AN:

10560

Middle Eastern (MID)

AF:

0.371

AC:

109

AN:

294

European-Non Finnish (NFE)

AF:

0.419

AC:

28432

AN:

67912

Other (OTH)

AF:

0.390

AC:

819

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1799

3598

5396

7195

8994

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

542

1084

1626

2168

2710

<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:

0.394

Hom.:

3950

Bravo

AF:

0.375

Asia WGS

AF:

0.286

AC:

993

AN:

3474

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (1)

Peroxisome biogenesis disorder 10A (Zellweger) (1)

Peroxisome biogenesis disorder 10B (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.68

PhyloP100

0.83

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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