Variant 12-7190262-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001351132.2(PEX5):c.-16-100G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0313 in 1,591,844 control chromosomes in the GnomAD database, including 926 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 78 hom., cov: 32)

Exomes 𝑓: 0.032 ( 848 hom. )

Consequence

PEX5
NM_001351132.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.121

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 12-7190262-G-A is Benign according to our data. Variant chr12-7190262-G-A is described in ClinVar as [Benign]. Clinvar id is 1291393.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0273 (4163/152268) while in subpopulation NFE AF= 0.0371 (2521/68000). AF 95% confidence interval is 0.0359. There are 78 homozygotes in gnomad4. There are 2146 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 78 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEX5	NM_001351132.2 linkuse as main transcript	c.-16-100G>A		intron_variant		ENST00000675855.1	NP_001338061.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEX5	ENST00000675855.1 linkuse as main transcript	c.-16-100G>A		intron_variant			NM_001351132.2	ENSP00000502374	A1	P50542-1

Frequencies

GnomAD3 genomes

AF:

0.0274

AC:

4166

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00572

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0312

Gnomad ASJ

AF:

0.0277

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00973

Gnomad FIN

AF:

0.0641

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0371

Gnomad OTH

AF:

0.0382

GnomAD4 exome

AF:

0.0317

AC:

45601

AN:

1439576

Hom.:

848

Cov.:

AF XY:

0.0313

AC XY:

22446

AN XY:

716728

show subpopulations

Gnomad4 AFR exome

AF:

0.00529

Gnomad4 AMR exome

AF:

0.0224

Gnomad4 ASJ exome

AF:

0.0313

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.0133

Gnomad4 FIN exome

AF:

0.0564

Gnomad4 NFE exome

AF:

0.0345

Gnomad4 OTH exome

AF:

0.0297

GnomAD4 genome

AF:

0.0273

AC:

4163

AN:

152268

Hom.:

Cov.:

AF XY:

0.0288

AC XY:

2146

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00570

Gnomad4 AMR

AF:

0.0311

Gnomad4 ASJ

AF:

0.0277

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00974

Gnomad4 FIN

AF:

0.0641

Gnomad4 NFE

AF:

0.0371

Gnomad4 OTH

AF:

0.0378

Alfa

AF:

0.0326

Hom.:

Bravo

AF:

0.0239

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 01, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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