chr2-61017848-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002618.4(PEX13):​c.89T>G​(p.Phe30Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000452 in 1,550,304 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F30S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PEX13
NM_002618.4 missense

Scores

2
6
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.06

Publications

1 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]
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19823408).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PEX13NM_002618.4 linkc.89T>G p.Phe30Cys missense_variant Exon 1 of 4 ENST00000295030.6 NP_002609.1 Q92968
PUS10NM_144709.4 linkc.-16+160A>C intron_variant Intron 1 of 17 ENST00000316752.11 NP_653310.2 Q3MIT2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PEX13ENST00000295030.6 linkc.89T>G p.Phe30Cys missense_variant Exon 1 of 4 1 NM_002618.4 ENSP00000295030.4 Q92968
PUS10ENST00000316752.11 linkc.-16+160A>C intron_variant Intron 1 of 17 1 NM_144709.4 ENSP00000326003.6 Q3MIT2

Frequencies

GnomAD3 genomes
AF:
0.0000328
AC:
5
AN:
152216
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
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:
0.00
GnomAD2 exomes
AF:
0.00000662
AC:
1
AN:
150968
AF XY:
0.0000124
show subpopulations
Gnomad AFR exome
AF:
0.000138
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
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:
0.00000143
AC:
2
AN:
1398088
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
689572
show subpopulations
African (AFR)
AF:
0.0000633
AC:
2
AN:
31588
American (AMR)
AF:
0.00
AC:
0
AN:
35684
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25174
East Asian (EAS)
AF:
0.00
AC:
0
AN:
35874
South Asian (SAS)
AF:
0.00
AC:
0
AN:
79210
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
48194
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5688
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1078708
Other (OTH)
AF:
0.00
AC:
0
AN:
57968
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.0000328
AC:
5
AN:
152216
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74368
show subpopulations
African (AFR)
AF:
0.000121
AC:
5
AN:
41456
American (AMR)
AF:
0.00
AC:
0
AN:
15282
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5200
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4838
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10618
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68034
Other (OTH)
AF:
0.00
AC:
0
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00
Hom.:
0
Bravo
AF:
0.0000529
ExAC
AF:
0.0000575
AC:
3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.43
BayesDel_addAF
Benign
-0.052
T
BayesDel_noAF
Uncertain
-0.060
CADD
Uncertain
25
DANN
Benign
0.96
DEOGEN2
Benign
0.40
.;T;D;T
Eigen
Benign
-0.11
Eigen_PC
Benign
-0.075
FATHMM_MKL
Benign
0.49
N
LIST_S2
Benign
0.41
T;T;T;T
M_CAP
Uncertain
0.15
D
MetaRNN
Benign
0.20
T;T;T;T
MetaSVM
Benign
-0.81
T
MutationAssessor
Benign
0.83
.;.;L;.
PhyloP100
2.1
PrimateAI
Pathogenic
0.83
D
PROVEAN
Pathogenic
-6.5
D;D;N;D
REVEL
Uncertain
0.45
Sift
Uncertain
0.011
.;.;D;.
Sift4G
Uncertain
0.0040
D;D;T;D
Polyphen
0.88
.;.;P;.
Vest4
0.50
MutPred
0.17
Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);
MVP
0.72
MPC
0.34
ClinPred
0.87
D
GERP RS
2.5
PromoterAI
0.065
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.23
gMVP
0.66
Mutation Taster
=67/33
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs771610641; hg19: chr2-61244983; API