6-42966762-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000287.4(PEX6):c.1961+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 1,613,236 control chromosomes in the GnomAD database, including 227,794 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 24944 hom., cov: 30)

Exomes 𝑓: 0.52 ( 202850 hom. )

Consequence

PEX6
NM_000287.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.00200

Publications

30 publications found

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 Gene-Disease associations (from GenCC):

peroxisome biogenesis disorder
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
peroxisome biogenesis disorder 4A (Zellweger)
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Myriad Women’s Health
peroxisome biogenesis disorder 4B
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
Heimler syndrome 2
Inheritance: AR Classification: MODERATE Submitted by: G2P
autosomal recessive cerebellar ataxia-blindness-deafness syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Zellweger spectrum disorders
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PEX6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 6-42966762-C-T is Benign according to our data. Variant chr6-42966762-C-T is described in ClinVar as Benign. ClinVar VariationId is 92781.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000287.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PEX6	NM_000287.4	MANE Select	c.1961+20G>A	intron	N/A	NP_000278.3
PEX6	NM_001316313.2		c.1697+20G>A	intron	N/A	NP_001303242.1	Q13608-3
PEX6	NR_133009.2		n.1992+20G>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PEX6	ENST00000304611.13	TSL:1 MANE Select	c.1961+20G>A	intron	N/A	ENSP00000303511.8	Q13608-1
PEX6	ENST00000244546.4	TSL:1	c.1961+20G>A	intron	N/A	ENSP00000244546.4	Q13608-2
PEX6	ENST00000858656.1		c.1961+20G>A	intron	N/A	ENSP00000528715.1

Frequencies

GnomAD3 genomes

AF:

0.559

AC:

84716

AN:

151614

Hom.:

24905

Cov.:

show subpopulations

Gnomad AFR

AF:

0.733

Gnomad AMI

AF:

0.671

Gnomad AMR

AF:

0.419

Gnomad ASJ

AF:

0.466

Gnomad EAS

AF:

0.183

Gnomad SAS

AF:

0.493

Gnomad FIN

AF:

0.465

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.536

Gnomad OTH

AF:

0.550

GnomAD2 exomes

AF:

0.478

AC:

120135

AN:

251462

AF XY:

0.485

show subpopulations

Gnomad AFR exome

AF:

0.735

Gnomad AMR exome

AF:

0.312

Gnomad ASJ exome

AF:

0.468

Gnomad EAS exome

AF:

0.197

Gnomad FIN exome

AF:

0.458

Gnomad NFE exome

AF:

0.531

Gnomad OTH exome

AF:

0.501

GnomAD4 exome

AF:

0.521

AC:

761019

AN:

1461502

Hom.:

202850

Cov.:

AF XY:

0.522

AC XY:

379231

AN XY:

727076

show subpopulations

African (AFR)

AF:

0.738

AC:

24700

AN:

33476

American (AMR)

AF:

0.331

AC:

14780

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.466

AC:

12172

AN:

26134

East Asian (EAS)

AF:

0.210

AC:

8343

AN:

39698

South Asian (SAS)

AF:

0.521

AC:

44975

AN:

86248

European-Finnish (FIN)

AF:

0.454

AC:

24255

AN:

53402

Middle Eastern (MID)

AF:

0.569

AC:

3282

AN:

5766

European-Non Finnish (NFE)

AF:

0.537

AC:

597367

AN:

1111674

Other (OTH)

AF:

0.516

AC:

31145

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

21845

43689

65534

87378

109223

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16834

33668

50502

67336

84170

<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:

0.559

AC:

84809

AN:

151734

Hom.:

24944

Cov.:

AF XY:

0.550

AC XY:

40786

AN XY:

74154

show subpopulations

African (AFR)

AF:

0.733

AC:

30313

AN:

41368

American (AMR)

AF:

0.419

AC:

6381

AN:

15220

Ashkenazi Jewish (ASJ)

AF:

0.466

AC:

1615

AN:

3466

East Asian (EAS)

AF:

0.183

AC:

940

AN:

5128

South Asian (SAS)

AF:

0.492

AC:

2367

AN:

4808

European-Finnish (FIN)

AF:

0.465

AC:

4901

AN:

10530

Middle Eastern (MID)

AF:

0.503

AC:

148

AN:

294

European-Non Finnish (NFE)

AF:

0.536

AC:

36384

AN:

67908

Other (OTH)

AF:

0.547

AC:

1149

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1789

3579

5368

7158

8947

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

718

1436

2154

2872

3590

<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:

0.539

Hom.:

12571

Bravo

AF:

0.562

Asia WGS

AF:

0.354

AC:

1234

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Heimler syndrome 2 (1)

Peroxisome biogenesis disorder (1)

Peroxisome biogenesis disorder 4A (Zellweger) (1)

Peroxisome biogenesis disorder 4B (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

9.3

(source)

DANN

Benign

0.49

PhyloP100

-0.0020

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over