17-35575211-TAA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_000286.3(PEX12):c.*569_*570del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0325 in 154,756 control chromosomes in the GnomAD database, including 101 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.033 (100 hom., cov: 32)
  • Exomes 𝑓: 0.031 (1 hom.)
• Consequence: PEX12 NM_000286.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0580

Genes affected

PEX12 (HGNC:8854): (peroxisomal biogenesis factor 12) This gene belongs to the peroxin-12 family. 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 Zellweger syndrome (ZWS). [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 17-35575211-TAA-T is Benign according to our data. Variant chr17-35575211-TAA-T is described in ClinVar as [Likely_benign]. Clinvar id is 322640.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0325 (4947/152078) while in subpopulation SAS AF= 0.0529 (255/4816). AF 95% confidence interval is 0.0476. There are 100 homozygotes in gnomad4. There are 2373 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 98 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEX12	NM_000286.3	c.*569_*570del		3_prime_UTR_variant	3/3	ENST00000225873.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEX12	ENST00000225873.9	c.*569_*570del		3_prime_UTR_variant	3/3	1	NM_000286.3	P1

Frequencies

GnomAD3 genomes AF: 0.0325 AC: 4937 AN: 151958 Hom.: 98 Cov.: 32

Gnomad AFR AF: 0.0287

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0407

Gnomad ASJ AF: 0.0415

Gnomad EAS AF: 0.0113

Gnomad SAS AF: 0.0527

Gnomad FIN AF: 0.0129

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0357

Gnomad OTH AF: 0.0407

GnomAD4 exome AF: 0.0306 AC: 82 AN: 2678 Hom.: 1 AF XY: 0.0309 AC XY: 44 AN XY: 1424

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.0172

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0478

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0326

Gnomad4 OTH exome AF: 0.0435

GnomAD4 genome AF: 0.0325 AC: 4947 AN: 152078 Hom.: 100 Cov.: 32 AF XY: 0.0319 AC XY: 2373 AN XY: 74330

Gnomad4 AFR AF: 0.0288

Gnomad4 AMR AF: 0.0406

Gnomad4 ASJ AF: 0.0415

Gnomad4 EAS AF: 0.0113

Gnomad4 SAS AF: 0.0529

Gnomad4 FIN AF: 0.0129

Gnomad4 NFE AF: 0.0357

Gnomad4 OTH AF: 0.0402

Alfa AF: 0.0325 Hom.: 4

Bravo AF: 0.0340

Asia WGS AF: 0.0310 AC: 110 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Peroxisome biogenesis disorder 1A (Zellweger) Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs3031851; hg19: chr17-33902230;