3-179898195-T-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_016559.3(PEX5L):c.145A>C(p.Ile49Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00074 in 1,613,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00049 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00077 ( 0 hom. )
Consequence
PEX5L
NM_016559.3 missense
NM_016559.3 missense
Scores
1
4
12
Clinical Significance
Conservation
PhyloP100: 4.67
Genes affected
PEX5L (HGNC:30024): (peroxisomal biogenesis factor 5 like) Enables peroxisome matrix targeting signal-1 binding activity and small GTPase binding activity. Predicted to be involved in protein import into peroxisome matrix, docking and regulation of cAMP-mediated signaling. Predicted to act upstream of or within maintenance of protein location and regulation of membrane potential. Located in cytosol. Part of receptor complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.024202466).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PEX5L | NM_016559.3 | c.145A>C | p.Ile49Leu | missense_variant | 3/15 | ENST00000467460.6 | |
PEX5L-AS2 | NR_110059.1 | n.2T>G | non_coding_transcript_exon_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PEX5L | ENST00000467460.6 | c.145A>C | p.Ile49Leu | missense_variant | 3/15 | 1 | NM_016559.3 | A1 | |
PEX5L-AS2 | ENST00000462801.2 | upstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000486 AC: 74AN: 152124Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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32
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GnomAD3 exomes AF: 0.000518 AC: 130AN: 251160Hom.: 0 AF XY: 0.000501 AC XY: 68AN XY: 135740
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GnomAD4 exome AF: 0.000766 AC: 1120AN: 1461354Hom.: 0 Cov.: 30 AF XY: 0.000704 AC XY: 512AN XY: 726992
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GnomAD4 genome ? AF: 0.000486 AC: 74AN: 152242Hom.: 0 Cov.: 32 AF XY: 0.000443 AC XY: 33AN XY: 74448
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ExAC
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 27, 2022 | The c.145A>C (p.I49L) alteration is located in exon 3 (coding exon 3) of the PEX5L gene. This alteration results from a A to C substitution at nucleotide position 145, causing the isoleucine (I) at amino acid position 49 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;.;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
T
PROVEAN
Benign
N;N;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T;.
Polyphen
0.0, 0.050
.;B;B;.;.;.;.
Vest4
MutPred
0.12
.;Gain of glycosylation at S54 (P = 0.0031);.;.;.;.;.;
MVP
MPC
0.40
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at