Variant rs2274517 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_000287.4(PEX6):c.2667-48G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 1,613,506 control chromosomes in the GnomAD database, including 229,140 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 25697 hom., cov: 32)

Exomes 𝑓: 0.52 ( 203443 hom. )

Consequence

PEX6
NM_000287.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0300

Variant links:

Genes affected

PEX6 (HGNC:8859): (peroxisomal biogenesis factor 6) This gene encodes a member of the AAA (ATPases associated with diverse cellular activities) family of ATPases. This member is a predominantly cytoplasmic protein, which plays a direct role in peroxisomal protein import and is required for PTS1 (peroxisomal targeting signal 1, a C-terminal tripeptide of the sequence ser-lys-leu) receptor activity. Mutations in this gene cause peroxisome biogenesis disorders of complementation group 4 and complementation group 6. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

PEX6 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=-0.81).

BP6

Variant 6-42964977-C-T is Benign according to our data. Variant chr6-42964977-C-T is described in ClinVar as [Benign]. Clinvar id is 1181155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEX6	NM_000287.4 linkuse as main transcript	c.2667-48G>A		intron_variant		ENST00000304611.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEX6	ENST00000304611.13 linkuse as main transcript	c.2667-48G>A		intron_variant		1	NM_000287.4	P1	Q13608-1
PEX6	ENST00000244546.4 linkuse as main transcript	c.*203-48G>A		intron_variant		1			Q13608-2

Frequencies

GnomAD3 genomes

AF:

0.565

AC:

85844

AN:

151922

Hom.:

25661

Cov.:

show subpopulations

Gnomad AFR

AF:

0.754

Gnomad AMI

AF:

0.675

Gnomad AMR

AF:

0.423

Gnomad ASJ

AF:

0.465

Gnomad EAS

AF:

0.183

Gnomad SAS

AF:

0.492

Gnomad FIN

AF:

0.466

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.536

Gnomad OTH

AF:

0.554

GnomAD3 exomes

AF:

0.480

AC:

120515

AN:

251274

Hom.:

31265

AF XY:

0.487

AC XY:

66076

AN XY:

135810

show subpopulations

Gnomad AFR exome

AF:

0.759

Gnomad AMR exome

AF:

0.314

Gnomad ASJ exome

AF:

0.468

Gnomad EAS exome

AF:

0.195

Gnomad SAS exome

AF:

0.513

Gnomad FIN exome

AF:

0.458

Gnomad NFE exome

AF:

0.531

Gnomad OTH exome

AF:

0.503

GnomAD4 exome

AF:

0.521

AC:

761788

AN:

1461466

Hom.:

203443

Cov.:

AF XY:

0.522

AC XY:

379545

AN XY:

727052

show subpopulations

Gnomad4 AFR exome

AF:

0.759

Gnomad4 AMR exome

AF:

0.332

Gnomad4 ASJ exome

AF:

0.466

Gnomad4 EAS exome

AF:

0.205

Gnomad4 SAS exome

AF:

0.522

Gnomad4 FIN exome

AF:

0.454

Gnomad4 NFE exome

AF:

0.537

Gnomad4 OTH exome

AF:

0.517

GnomAD4 genome

AF:

0.565

AC:

85933

AN:

152040

Hom.:

25697

Cov.:

AF XY:

0.556

AC XY:

41325

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.754

Gnomad4 AMR

AF:

0.423

Gnomad4 ASJ

AF:

0.465

Gnomad4 EAS

AF:

0.184

Gnomad4 SAS

AF:

0.492

Gnomad4 FIN

AF:

0.466

Gnomad4 NFE

AF:

0.536

Gnomad4 OTH

AF:

0.550

Alfa

AF:

0.534

Hom.:

7314

Bravo

AF:

0.569

Asia WGS

AF:

0.355

AC:

1237

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Peroxisome biogenesis disorder 4A (Zellweger)

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Heimler syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 07, 2018

- -

Peroxisome biogenesis disorder 4B

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.7

DANN

Benign

0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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