rs2820421

Variant names:

• chr1-160286214-C-A
• rs2820421
• ENST00000533699.5:n.64+71G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.228
• Publications: 23 publications found

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

ENSG00000298580 (HGNC:):

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000533699.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX19	ENST00000533699.5	TSL:4	n.64+71G>T		intron	N/A
	ENSG00000298580	ENST00000756649.1		n.481+1359C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97668 AN: 151958 Hom.: 32913 Cov.: 32

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: 20 AN: 34 Hom.: 6 AF XY: 0.550 AC XY: 11 AN XY: 20

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 3 AN: 6

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.615 AC: 16 AN: 26

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.643 AC: 97776 AN: 152076 Hom.: 32962 Cov.: 32 AF XY: 0.640 AC XY: 47557 AN XY: 74336

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.5
DANN	Benign	0.81
PhyloP100		0.23

Splicing

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

Other links and lift over

dbSNP: rs2820421; hg19: chr1-160256004;