Variant chr17-35575211-TAA-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

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

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0580

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 -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 GnomAd4 at 100 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEX12	NM_000286.3 linkuse as main transcript	c.569_570del		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.569_570del		3_prime_UTR_variant	3/3	1	NM_000286.3	ENSP00000225873	P1

Frequencies

GnomAD3 genomes

AF:

0.0325

AC:

4937

AN:

151958

Hom.:

Cov.:

show subpopulations

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:

AN:

2678

Hom.:

AF XY:

0.0309

AC XY:

AN XY:

1424

show subpopulations

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.:

AF XY:

0.0319

AC XY:

2373

AN XY:

74330

show subpopulations

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.:

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

LINK: link

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

Name

Calibrated prediction

Score

Prediction

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