rs11586985

Variant names:

Variant summary

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

The NM_002617.4(PEX10):c.913-4G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,586,640 control chromosomes in the GnomAD database, including 9,839 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.088 ( 809 hom., cov: 34)

Exomes 𝑓: 0.11 ( 9030 hom. )

Consequence

PEX10
NM_002617.4 splice_region, intron

Scores

Splicing: ADA: 0.00004033

Clinical Significance

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

Conservation

PhyloP100: -1.60

Publications

12 publications found

Variant links:

Genes affected

PEX10 (HGNC:8851): (peroxisomal biogenesis factor 10) This gene encodes a protein involved in import of peroxisomal matrix proteins. This protein localizes to the peroxisomal membrane. Mutations in this gene result in phenotypes within the Zellweger spectrum of peroxisomal biogenesis disorders, ranging from neonatal adrenoleukodystrophy to Zellweger syndrome. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

PEX10 Gene-Disease associations (from GenCC):

peroxisome biogenesis disorder
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
peroxisome biogenesis disorder 6A (Zellweger)
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Myriad Women’s Health
peroxisome biogenesis disorder 6B
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
autosomal recessive ataxia due to PEX10 deficiency
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Zellweger spectrum disorders
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PEX10 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=-0.87).

BP6

Variant 1-2405838-C-T is Benign according to our data. Variant chr1-2405838-C-T is described in ClinVar as Benign. ClinVar VariationId is 262791.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX10	NM_002617.4 link	c.913-4G>A		splice_region_variant, intron_variant	Intron 5 of 5	ENST00000447513.7	NP_002608.1	O60683-1A0A024R068

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PEX10	ENST00000447513.7 link	c.913-4G>A	splice_region_variant, intron_variant	Intron 5 of 5	1	NM_002617.4	ENSP00000407922.2	O60683-1
PEX10	ENST00000288774.8 link	c.973-4G>A	splice_region_variant, intron_variant	Intron 5 of 5	1		ENSP00000288774.3	O60683-2
PEX10	ENST00000507596.5 link	c.913-10G>A	intron_variant	Intron 5 of 5	5		ENSP00000424291.1	D6RBB0
PEX10	ENST00000650293.1 link	n.865-4G>A	splice_region_variant, intron_variant	Intron 5 of 7			ENSP00000497980.1	A0A3B3ITN6

Frequencies

GnomAD3 genomes

AF:

0.0878

AC:

13368

AN:

152218

Hom.:

808

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0222

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.0801

Gnomad ASJ

AF:

0.127

Gnomad EAS

AF:

0.116

Gnomad SAS

AF:

0.101

Gnomad FIN

AF:

0.127

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.118

Gnomad OTH

AF:

0.109

GnomAD2 exomes

AF:

0.105

AC:

21178

AN:

201770

AF XY:

0.108

show subpopulations

Gnomad AFR exome

AF:

0.0217

Gnomad AMR exome

AF:

0.0584

Gnomad ASJ exome

AF:

0.116

Gnomad EAS exome

AF:

0.122

Gnomad FIN exome

AF:

0.124

Gnomad NFE exome

AF:

0.122

Gnomad OTH exome

AF:

0.120

GnomAD4 exome

AF:

0.110

AC:

157972

AN:

1434304

Hom.:

9030

Cov.:

AF XY:

0.111

AC XY:

78588

AN XY:

711104

show subpopulations

African (AFR)

AF:

0.0212

AC:

696

AN:

32858

American (AMR)

AF:

0.0617

AC:

2544

AN:

41220

Ashkenazi Jewish (ASJ)

AF:

0.120

AC:

3062

AN:

25622

East Asian (EAS)

AF:

0.0914

AC:

3487

AN:

38138

South Asian (SAS)

AF:

0.109

AC:

8985

AN:

82292

European-Finnish (FIN)

AF:

0.128

AC:

6419

AN:

50236

Middle Eastern (MID)

AF:

0.200

AC:

1135

AN:

5664

European-Non Finnish (NFE)

AF:

0.114

AC:

124988

AN:

1098884

Other (OTH)

AF:

0.112

AC:

6656

AN:

59390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

6400

12800

19200

25600

32000

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4440

8880

13320

17760

22200

<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:

0.0878

AC:

13368

AN:

152336

Hom.:

809

Cov.:

AF XY:

0.0888

AC XY:

6617

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.0221

AC:

920

AN:

41584

American (AMR)

AF:

0.0799

AC:

1223

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

441

AN:

3470

East Asian (EAS)

AF:

0.117

AC:

608

AN:

5188

South Asian (SAS)

AF:

0.101

AC:

489

AN:

4828

European-Finnish (FIN)

AF:

0.127

AC:

1347

AN:

10616

Middle Eastern (MID)

AF:

0.245

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.118

AC:

7995

AN:

68024

Other (OTH)

AF:

0.111

AC:

234

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

622

1244

1865

2487

3109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

154

308

462

616

770

<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:

0.0815

Hom.:

249

Bravo

AF:

0.0813

Asia WGS

AF:

0.110

AC:

381

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Oct 21, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Sep 26, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Peroxisome biogenesis disorder 6A (Zellweger)

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Jul 08, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Peroxisome biogenesis disorder 6B

Benign:1

Jul 08, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Zellweger spectrum disorders

Benign:1

Nov 21, 2019

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Peroxisome biogenesis disorder, complementation group 7

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.20

(source)

DANN

Benign

0.61

PhyloP100

-1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000040

dbscSNV1_RF

Benign

0.0020

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over