17-35575229-TAAC-T

Position:

• chr17-35575229-TAAC-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000286.3(PEX12):​c.*550_*552del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0237 in 155,410 control chromosomes in the GnomAD database, including 123 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (121 hom., cov: 32)
  • Exomes 𝑓: 0.020 (2 hom.)
• Consequence: PEX12 NM_000286.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.903

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 17-35575229-TAAC-T is Benign according to our data. Variant chr17-35575229-TAAC-T is described in ClinVar as [Likely_benign]. Clinvar id is 322642.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEX12	NM_000286.3	c.*550_*552del		3_prime_UTR_variant	3/3	ENST00000225873.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEX12	ENST00000225873.9	c.*550_*552del		3_prime_UTR_variant	3/3	1	NM_000286.3	P1

Frequencies

GnomAD3 genomes AF: 0.0238 AC: 3623 AN: 152168 Hom.: 122 Cov.: 32

Gnomad AFR AF: 0.00632

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00825

Gnomad ASJ AF: 0.0109

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.0481

Gnomad FIN AF: 0.0393

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0235

Gnomad OTH AF: 0.0143

GnomAD4 exome AF: 0.0195 AC: 61 AN: 3124 Hom.: 2 AF XY: 0.0177 AC XY: 29 AN XY: 1638

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0177

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.186

Gnomad4 SAS exome AF: 0.0248

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.0124

Gnomad4 OTH exome AF: 0.0273

GnomAD4 genome AF: 0.0238 AC: 3619 AN: 152286 Hom.: 121 Cov.: 32 AF XY: 0.0258 AC XY: 1923 AN XY: 74438

Gnomad4 AFR AF: 0.00630

Gnomad4 AMR AF: 0.00824

Gnomad4 ASJ AF: 0.0109

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.0477

Gnomad4 FIN AF: 0.0393

Gnomad4 NFE AF: 0.0235

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.0229 Hom.: 7

Bravo AF: 0.0214

Asia WGS AF: 0.0910 AC: 315 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

- -

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: rs147182821; hg19: chr17-33902248;