dbSNP rs2820421: PEX19:n.64+71G>T (chr1-160286214-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000533699.5(PEX19):n.64+71G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 152,110 control chromosomes in the GnomAD database, including 32,968 homozygotes. 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 0.64 ( 32962 hom., cov: 32)

Exomes 𝑓: 0.59 ( 6 hom. )

Consequence

PEX19
ENST00000533699.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.228

Publications

23 publications found

Variant links:

Genes affected

PEX19 (HGNC:9713): (peroxisomal biogenesis factor 19) This gene is necessary for early peroxisomal biogenesis. It acts both as a cytosolic chaperone and as an import receptor for peroxisomal membrane proteins (PMPs). 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. These disorders have at least 14 complementation groups, with more than one phenotype being observed for some 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 Zellweger syndrome (ZWS), as well as peroxisome biogenesis disorder complementation group 14 (PBD-CG14), which is also known as PBD-CGJ. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2010]

PEX19 Gene-Disease associations (from GenCC):

peroxisome biogenesis disorder
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
peroxisome biogenesis disorder 12A (Zellweger)
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
Zellweger spectrum disorders
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PEX19 links:

ENSG00000298580 (HGNC:):

ENSG00000298580 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC107985219	XR_001738265.2 link	n.492-103C>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX19	ENST00000533699.5 link	n.64+71G>T		intron_variant	Intron 1 of 4	4
ENSG00000298580	ENST00000756649.1 link	n.481+1359C>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.643

AC:

97668

AN:

151958

Hom.:

32913

Cov.:

show subpopulations

Gnomad AFR

AF:

0.863

Gnomad AMI

AF:

0.596

Gnomad AMR

AF:

0.575

Gnomad ASJ

AF:

0.502

Gnomad EAS

AF:

0.464

Gnomad SAS

AF:

0.704

Gnomad FIN

AF:

0.552

Gnomad MID

AF:

0.675

Gnomad NFE

AF:

0.555

Gnomad OTH

AF:

0.637

GnomAD4 exome

AF:

0.588

AC:

AN:

Hom.:

AF XY:

0.550

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.615

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.643

AC:

97776

AN:

152076

Hom.:

32962

Cov.:

AF XY:

0.640

AC XY:

47557

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.863

AC:

35805

AN:

41496

American (AMR)

AF:

0.575

AC:

8789

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.502

AC:

1741

AN:

3470

East Asian (EAS)

AF:

0.464

AC:

2399

AN:

5170

South Asian (SAS)

AF:

0.702

AC:

3380

AN:

4816

European-Finnish (FIN)

AF:

0.552

AC:

5833

AN:

10560

Middle Eastern (MID)

AF:

0.685

AC:

200

AN:

292

European-Non Finnish (NFE)

AF:

0.555

AC:

37740

AN:

67968

Other (OTH)

AF:

0.639

AC:

1348

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1656

3312

4967

6623

8279

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.578

Hom.:

22349

Bravo

AF:

0.654

Asia WGS

AF:

0.630

AC:

2193

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.5

(source)

DANN

Benign

0.81

PhyloP100

0.23

Splicing

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.

rs2820421

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over