rs764069625

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_002618.4(PEX13):c.26C>A(p.Pro9His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000903 in 1,550,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. P9R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000086 ( 0 hom. )

Consequence

PEX13
NM_002618.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 2.94

Publications

0 publications found

Variant links:

Genes affected

PEX13 (HGNC:8855): (peroxisomal biogenesis factor 13) This gene encodes a peroxisomal membrane protein that binds the type 1 peroxisomal targeting signal receptor via a SH3 domain located in the cytoplasm. Mutations and deficiencies in peroxisomal protein importing and peroxisome assembly lead to peroxisomal biogenesis disorders, an example of which is Zellweger syndrome. [provided by RefSeq, Oct 2008]

PEX13 links:

PUS10 (HGNC:26505): (pseudouridine synthase 10) Pseudouridination, the isomerization of uridine to pseudouridine, is the most common posttranscriptional nucleotide modification found in RNA and is essential for biologic functions such as spliceosome biogenesis. Pseudouridylate synthases, such as PUS10, catalyze pseudouridination of structural RNAs, including transfer, ribosomal, and splicing RNAs. These enzymes also act as RNA chaperones, facilitating the correct folding and assembly of tRNAs (McCleverty et al., 2007 [PubMed 17900615]).[supplied by OMIM, May 2009]

PUS10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3159654).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002618.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PEX13	NM_002618.4	MANE Select	c.26C>A	p.Pro9His	missense	Exon 1 of 4	NP_002609.1	Q92968
PUS10	NM_144709.4	MANE Select	c.-16+223G>T		intron	N/A	NP_653310.2	Q3MIT2
PUS10	NM_001322127.1		c.-623+223G>T		intron	N/A	NP_001309056.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PEX13	ENST00000295030.6	TSL:1 MANE Select	c.26C>A	p.Pro9His	missense	Exon 1 of 4	ENSP00000295030.4	Q92968
PEX13	ENST00000444100.2	TSL:1	c.26C>A	p.Pro9His	missense	Exon 1 of 2	ENSP00000405184.2	D3YTD3
PEX13	ENST00000414712.2	TSL:1	c.26C>A	p.Pro9His	missense	Exon 1 of 2	ENSP00000405413.2	G5E9N6

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152234

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00000660

AC:

AN:

151550

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000119

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000858

AC:

AN:

1397976

Hom.:

Cov.:

AF XY:

0.00000580

AC XY:

AN XY:

689472

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31596

American (AMR)

AF:

0.0000281

AC:

AN:

35632

Ashkenazi Jewish (ASJ)

AF:

0.0000397

AC:

AN:

25168

East Asian (EAS)

AF:

0.00

AC:

AN:

35878

South Asian (SAS)

AF:

0.00

AC:

AN:

79136

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48180

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5576

European-Non Finnish (NFE)

AF:

0.00000742

AC:

AN:

1078856

Other (OTH)

AF:

0.0000345

AC:

AN:

57954

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

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:

0.0000131

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74376

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000241

AC:

AN:

41456

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68042

Other (OTH)

AF:

0.000478

AC:

AN:

2094

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

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:

0.0000165

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000200

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Peroxisome biogenesis disorder 11A (Zellweger) (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Uncertain

0.044

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.38

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.46

M_CAP

Pathogenic

0.40

MetaRNN

Benign

0.32

MetaSVM

Uncertain

-0.0057

MutationAssessor

Benign

0.90

PhyloP100

2.9

PrimateAI

Uncertain

0.79

PROVEAN

Pathogenic

-7.0

REVEL

Uncertain

0.34

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.32

MVP

0.83

MPC

0.50

ClinPred

0.96

GERP RS

4.8

PromoterAI

-0.026

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.46

gMVP

0.50

Mutation Taster

=79/21

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