17-35578726-C-T

Position:

• chr17-35578726-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000585380.1(PEX12):​c.-97G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 156,576 control chromosomes in the GnomAD database, including 17,895 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (17422 hom., cov: 33)
  • Exomes 𝑓: 0.44 (473 hom.)
• Consequence: PEX12 ENST00000585380.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.935

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]

AP2B1 (HGNC:563): (adaptor related protein complex 2 subunit beta 1) The protein encoded by this gene is one of two large chain components of the assembly protein complex 2, which serves to link clathrin to receptors in coated vesicles. The encoded protein is found on the cytoplasmic face of coated vesicles in the plasma membrane. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 17-35578726-C-T is Benign according to our data. Variant chr17-35578726-C-T is described in ClinVar as [Benign]. Clinvar id is 1230466.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.35578726C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEX12	ENST00000585380.1	c.-97G>A		5_prime_UTR_variant	1/3	4		ENSP00000466280.1
AP2B1	ENST00000589774.5	c.-24+605C>T		intron_variant		4		ENSP00000468183.1

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72631 AN: 151998 Hom.: 17429 Cov.: 33

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.463

GnomAD4 exome AF: 0.440 AC: 1964 AN: 4460 Hom.: 473 Cov.: 0 AF XY: 0.438 AC XY: 1074 AN XY: 2450

Gnomad4 AFR exome AF: 0.417

Gnomad4 AMR exome AF: 0.444

Gnomad4 ASJ exome AF: 0.571

Gnomad4 EAS exome AF: 0.510

Gnomad4 SAS exome AF: 0.393

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.452

Gnomad4 OTH exome AF: 0.335

GnomAD4 genome AF: 0.478 AC: 72637 AN: 152116 Hom.: 17422 Cov.: 33 AF XY: 0.480 AC XY: 35712 AN XY: 74346

Gnomad4 AFR AF: 0.434

Gnomad4 AMR AF: 0.508

Gnomad4 ASJ AF: 0.375

Gnomad4 EAS AF: 0.520

Gnomad4 SAS AF: 0.436

Gnomad4 FIN AF: 0.506

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.459

Alfa AF: 0.482 Hom.: 29726

Bravo AF: 0.472

Asia WGS AF: 0.459 AC: 1593 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	Aug 07, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.95
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs321599; hg19: chr17-33905745;