15-89683684-A-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BS2
The NM_003847.3(PEX11A):c.437T>G(p.Met146Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000227 in 1,614,132 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00023 ( 1 hom. )
Consequence
PEX11A
NM_003847.3 missense
NM_003847.3 missense
Scores
8
6
5
Clinical Significance
Conservation
PhyloP100: 8.77
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_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BS2
?
High Homozygotes in GnomAdExome at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PEX11A | NM_003847.3 | c.437T>G | p.Met146Arg | missense_variant | 3/3 | ENST00000300056.8 | |
PEX11A | NM_001271573.2 | c.2T>G | p.Met1? | start_lost | 2/2 | ||
PEX11A | NM_001271572.2 | c.344T>G | p.Met115Arg | missense_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PEX11A | ENST00000300056.8 | c.437T>G | p.Met146Arg | missense_variant | 3/3 | 1 | NM_003847.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000158 AC: 24AN: 152218Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000310 AC: 78AN: 251384Hom.: 2 AF XY: 0.000302 AC XY: 41AN XY: 135868
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GnomAD4 exome AF: 0.000234 AC: 342AN: 1461796Hom.: 1 Cov.: 32 AF XY: 0.000216 AC XY: 157AN XY: 727208
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GnomAD4 genome ? AF: 0.000158 AC: 24AN: 152336Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74486
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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 | Dec 28, 2022 | The c.437T>G (p.M146R) alteration is located in exon 3 (coding exon 3) of the PEX11A gene. This alteration results from a T to G substitution at nucleotide position 437, causing the methionine (M) at amino acid position 146 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Pathogenic
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
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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