Genetic Variant PEX12:c.*550_*552delGTT (chr17-35575229-TAAC-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000286.3(PEX12):c.*550_*552delGTT 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

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.903

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PEX12	NM_000286.3 link	c.550_552delGTT		3_prime_UTR_variant	Exon 3 of 3	ENST00000225873.9	NP_000277.1	O00623

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX12	ENST00000225873 link	c.550_552delGTT		3_prime_UTR_variant	Exon 3 of 3	1	NM_000286.3	ENSP00000225873.3		O00623

Frequencies

GnomAD3 genomes

AF:

0.0238

AC:

3623

AN:

152168

Hom.:

122

Cov.:

show subpopulations

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:

AN:

3124

Hom.:

AF XY:

0.0177

AC XY:

AN XY:

1638

show subpopulations

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

Gnomad4 AMR exome

AF:

0.0177

AC:

AN:

734

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

Gnomad4 EAS exome

AF:

0.186

AC:

AN:

Gnomad4 SAS exome

AF:

0.0248

AC:

AN:

322

Gnomad4 FIN exome

AF:

0.100

AC:

AN:

Gnomad4 NFE exome

AF:

0.0124

AC:

AN:

1856

Gnomad4 Remaining exome

AF:

0.0273

AC:

AN:

110

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0238

AC:

3619

AN:

152286

Hom.:

121

Cov.:

AF XY:

0.0258

AC XY:

1923

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00630

AC:

0.00630141

AN:

0.00630141

Gnomad4 AMR

AF:

0.00824

AC:

0.00823745

AN:

0.00823745

Gnomad4 ASJ

AF:

0.0109

AC:

0.0109447

AN:

0.0109447

Gnomad4 EAS

AF:

0.178

AC:

0.177825

AN:

0.177825

Gnomad4 SAS

AF:

0.0477

AC:

0.0476981

AN:

0.0476981

Gnomad4 FIN

AF:

0.0393

AC:

0.0393322

AN:

0.0393322

Gnomad4 NFE

AF:

0.0235

AC:

0.0234609

AN:

0.0234609

Gnomad4 OTH

AF:

0.0147

AC:

0.0146641

AN:

0.0146641

Heterozygous variant carriers

179

359

538

718

897

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0229

Hom.:

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

LINK: link

Submissions by phenotype

Peroxisome biogenesis disorder 1A (Zellweger)

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=100/0

polymorphism (auto)

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