1-2405770-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002617.4(PEX10):c.977G>A(p.Arg326His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000868 in 1,601,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R326S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000094 ( 0 hom. )

Consequence

PEX10
NM_002617.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:5

Conservation

PhyloP100: 2.40

Publications

0 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: Myriad Women’s Health, Ambry Genetics, G2P
peroxisome biogenesis disorder 6B
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, 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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1530948).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002617.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PEX10	NM_002617.4	MANE Select	c.977G>A	p.Arg326His	missense	Exon 6 of 6	NP_002608.1	O60683-1
PEX10	NM_153818.2		c.1037G>A	p.Arg346His	missense	Exon 6 of 6	NP_722540.1	O60683-2
PEX10	NM_001374425.1		c.1034G>A	p.Arg345His	missense	Exon 6 of 6	NP_001361354.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PEX10	ENST00000447513.7	TSL:1 MANE Select	c.977G>A	p.Arg326His	missense	Exon 6 of 6	ENSP00000407922.2	O60683-1
PEX10	ENST00000288774.8	TSL:1	c.1037G>A	p.Arg346His	missense	Exon 6 of 6	ENSP00000288774.3	O60683-2
PEX10	ENST00000874692.1		c.1034G>A	p.Arg345His	missense	Exon 6 of 6	ENSP00000544751.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152276

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000309

AC:

AN:

226464

AF XY:

0.0000326

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000306

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000593

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000939

AC:

136

AN:

1449082

Hom.:

Cov.:

AF XY:

0.0000945

AC XY:

AN XY:

719668

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33160

American (AMR)

AF:

0.0000231

AC:

AN:

43314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25874

East Asian (EAS)

AF:

0.000385

AC:

AN:

39002

South Asian (SAS)

AF:

0.0000119

AC:

AN:

83822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51956

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.000105

AC:

116

AN:

1106368

Other (OTH)

AF:

0.0000501

AC:

AN:

59836

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0000197

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41478

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000192

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68054

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.0000522

Hom.:

Bravo

AF:

0.0000189

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000828

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Peroxisome biogenesis disorder 6A (Zellweger);C3553948:Peroxisome biogenesis disorder 6B (2)

Inborn genetic diseases (1)

Peroxisome biogenesis disorder 6A (Zellweger) (1)

Peroxisome biogenesis disorder, complementation group 7 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.024

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Benign

-0.029

Eigen_PC

Benign

-0.015

FATHMM_MKL

Benign

0.58

LIST_S2

Uncertain

0.93

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.15

MetaSVM

Uncertain

-0.19

MutationAssessor

Benign

1.0

PhyloP100

2.4

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.1

REVEL

Benign

0.23

Sift

Uncertain

0.014

Sift4G

Uncertain

0.015

Polyphen

1.0

Vest4

0.26

MVP

0.78

MPC

0.54

ClinPred

0.31

GERP RS

3.9

Varity_R

0.16

gMVP

0.44

Mutation Taster

=89/11

polymorphism

(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