12-7189901-G-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS1

The NM_001131025.2(PEX5):c.-332G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000684 in 1,418,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

PEX5
NM_001131025.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.190

Publications

0 publications found

Variant links:

Genes affected

PEX5 (HGNC:9719): (peroxisomal biogenesis factor 5) The product of this gene binds to the C-terminal PTS1-type tripeptide peroxisomal targeting signal (SKL-type) and plays an essential role in peroxisomal protein import. 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 of neonatal adrenoleukodystrophy (NALD), a cause of Zellweger syndrome (ZWS) as well as may be a cause of infantile Refsum disease (IRD). Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2008]

PEX5 Gene-Disease associations (from GenCC):

peroxisome biogenesis disorder
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
peroxisome biogenesis disorder 2A (Zellweger)
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
peroxisome biogenesis disorder 2B
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
rhizomelic chondrodysplasia punctata type 5
Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
Zellweger spectrum disorders
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PEX5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000368 (56/152326) while in subpopulation AFR AF = 0.00132 (55/41574). AF 95% confidence interval is 0.00104. There are 0 homozygotes in GnomAd4. There are 29 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001131025.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PEX5	NM_001351132.2	MANE Select	c.-17+151G>T	intron	N/A	NP_001338061.1	P50542-1
PEX5	NM_001131025.2		c.-332G>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 16	NP_001124497.1	A0A0S2Z4H1
PEX5	NM_001300789.3		c.-96G>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 16	NP_001287718.2	A0A0S2Z4H1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PEX5	ENST00000420616.6	TSL:1	c.-332G>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 16	ENSP00000410159.2	P50542-1
PEX5	ENST00000420616.6	TSL:1	c.-332G>T	5_prime_UTR	Exon 1 of 16	ENSP00000410159.2	P50542-1
PEX5	ENST00000675855.1	MANE Select	c.-17+151G>T	intron	N/A	ENSP00000502374.1	P50542-1

Frequencies

GnomAD3 genomes

AF:

0.000368

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000109

AC:

AN:

45774

AF XY:

0.0000773

show subpopulations

Gnomad AFR exome

AF:

0.00168

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000324

AC:

AN:

1266424

Hom.:

Cov.:

AF XY:

0.0000260

AC XY:

AN XY:

615082

show subpopulations

African (AFR)

AF:

0.00137

AC:

AN:

26360

American (AMR)

AF:

0.0000731

AC:

AN:

13678

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19786

East Asian (EAS)

AF:

0.00

AC:

AN:

31228

South Asian (SAS)

AF:

0.00

AC:

AN:

60126

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31498

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4730

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1026468

Other (OTH)

AF:

0.0000761

AC:

AN:

52550

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000368

AC:

AN:

152326

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.00132

AC:

AN:

41574

American (AMR)

AF:

0.00

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000365

Hom.:

Bravo

AF:

0.000419

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

7.4

(source)

DANN

Benign

0.89

PhyloP100

0.19

PromoterAI

-0.11

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.2

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

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