Variant chr17-35575616-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000286.3(PEX12):c.*166C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 724,962 control chromosomes in the GnomAD database, including 15,322 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3374 hom., cov: 32)

Exomes 𝑓: 0.20 ( 11948 hom. )

Consequence

PEX12
NM_000286.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.396

Variant links:

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]

PEX12 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 17-35575616-G-T is Benign according to our data. Variant chr17-35575616-G-T is described in ClinVar as [Benign]. Clinvar id is 322651.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEX12	NM_000286.3 linkuse as main transcript	c.*166C>A		3_prime_UTR_variant	3/3	ENST00000225873.9	NP_000277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEX12	ENST00000225873.9 linkuse as main transcript	c.*166C>A		3_prime_UTR_variant	3/3	1	NM_000286.3	ENSP00000225873	P1

Frequencies

GnomAD3 genomes

AF:

0.207

AC:

31444

AN:

151920

Hom.:

3368

Cov.:

show subpopulations

Gnomad AFR

AF:

0.246

Gnomad AMI

AF:

0.113

Gnomad AMR

AF:

0.226

Gnomad ASJ

AF:

0.249

Gnomad EAS

AF:

0.333

Gnomad SAS

AF:

0.204

Gnomad FIN

AF:

0.176

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.173

Gnomad OTH

AF:

0.217

GnomAD4 exome

AF:

0.198

AC:

113329

AN:

572924

Hom.:

11948

Cov.:

AF XY:

0.198

AC XY:

60371

AN XY:

305284

show subpopulations

Gnomad4 AFR exome

AF:

0.243

Gnomad4 AMR exome

AF:

0.239

Gnomad4 ASJ exome

AF:

0.238

Gnomad4 EAS exome

AF:

0.356

Gnomad4 SAS exome

AF:

0.204

Gnomad4 FIN exome

AF:

0.168

Gnomad4 NFE exome

AF:

0.176

Gnomad4 OTH exome

AF:

0.207

GnomAD4 genome

AF:

0.207

AC:

31477

AN:

152038

Hom.:

3374

Cov.:

AF XY:

0.209

AC XY:

15502

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.246

Gnomad4 AMR

AF:

0.225

Gnomad4 ASJ

AF:

0.249

Gnomad4 EAS

AF:

0.334

Gnomad4 SAS

AF:

0.204

Gnomad4 FIN

AF:

0.176

Gnomad4 NFE

AF:

0.173

Gnomad4 OTH

AF:

0.221

Alfa

AF:

0.187

Hom.:

4584

Bravo

AF:

0.216

Asia WGS

AF:

0.275

AC:

960

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 17, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Peroxisome biogenesis disorder 3A (Zellweger)

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

2.4

DANN

Benign

0.73

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over