2-61017848-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002618.4(PEX13):ā€‹c.89T>Gā€‹(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.

Frequency

Genomes: š‘“ 0.000033 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

PEX13
NM_002618.4 missense

Scores

2
6
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.06
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 made for transcript

Verdict is Uncertain_significance. Variant got 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
GnomAD3 exomes
AF:
0.00000662
AC:
1
AN:
150968
Hom.:
0
AF XY:
0.0000124
AC XY:
1
AN XY:
80712
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 SAS 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
Gnomad4 AFR exome
AF:
0.0000633
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
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
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
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;.
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
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.23
gMVP
0.66

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs771610641; hg19: chr2-61244983; API