15-89686436-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_003847.3(PEX11A):c.167G>A(p.Arg56His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000269 in 1,449,338 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000025 ( 0 hom. )
Consequence
PEX11A
NM_003847.3 missense
NM_003847.3 missense
Scores
10
4
3
Clinical Significance
Conservation
PhyloP100: 7.34
Genes affected
PEX11A (HGNC:8852): (peroxisomal biogenesis factor 11 alpha) This gene is a member of the PEX11 family, which is composed of membrane elongation factors involved in regulation of peroxisome maintenance and proliferation. This gene product interacts with peroxisomal membrane protein 19 and may respond to outside stimuli to increase peroxisome abundance. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2012]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.949
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PEX11A | NM_003847.3 | c.167G>A | p.Arg56His | missense_variant | 2/3 | ENST00000300056.8 | |
PEX11A | NM_001271572.2 | c.167G>A | p.Arg56His | missense_variant | 2/3 | ||
PEX11A | NM_001271573.2 | c.-263-2488G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PEX11A | ENST00000300056.8 | c.167G>A | p.Arg56His | missense_variant | 2/3 | 1 | NM_003847.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152182Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000280 AC: 7AN: 249610Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 134950
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GnomAD4 exome AF: 0.0000247 AC: 32AN: 1297156Hom.: 0 Cov.: 19 AF XY: 0.0000229 AC XY: 15AN XY: 653854
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74340
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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 | Feb 13, 2023 | The c.167G>A (p.R56H) alteration is located in exon 2 (coding exon 2) of the PEX11A gene. This alteration results from a G to A substitution at nucleotide position 167, causing the arginine (R) at amino acid position 56 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
Sift
Pathogenic
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
1.0
.;D;.
Vest4
MVP
MPC
0.20
ClinPred
D
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