15-89683735-T-C

Variant summary

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

The NM_001271573.2(PEX11A):​c.-50A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

PEX11A
NM_001271573.2 5_prime_UTR_premature_start_codon_gain

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.642
Variant links:
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 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=0.10247132).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PEX11ANM_003847.3 linkuse as main transcriptc.386A>G p.Tyr129Cys missense_variant 3/3 ENST00000300056.8 NP_003838.1 O75192-1B2R8C6
PEX11ANM_001271573.2 linkuse as main transcriptc.-50A>G 5_prime_UTR_premature_start_codon_gain_variant 2/2 NP_001258502.1 B2R8C6B4DMF6
PEX11ANM_001271572.2 linkuse as main transcriptc.293A>G p.Tyr98Cys missense_variant 3/3 NP_001258501.1 O75192-2B2R8C6
PEX11ANM_001271573.2 linkuse as main transcriptc.-50A>G 5_prime_UTR_variant 2/2 NP_001258502.1 B2R8C6B4DMF6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PEX11AENST00000300056.8 linkuse as main transcriptc.386A>G p.Tyr129Cys missense_variant 3/31 NM_003847.3 ENSP00000300056.3 O75192-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152116
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000958
AC:
14
AN:
1461634
Hom.:
0
Cov.:
32
AF XY:
0.00000963
AC XY:
7
AN XY:
727116
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000989
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152116
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74294
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsMar 18, 2024The c.386A>G (p.Y129C) alteration is located in exon 3 (coding exon 3) of the PEX11A gene. This alteration results from a A to G substitution at nucleotide position 386, causing the tyrosine (Y) at amino acid position 129 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.067
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
9.9
DANN
Benign
0.72
DEOGEN2
Benign
0.34
T;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.32
N
LIST_S2
Benign
0.64
T;T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.10
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.2
M;.
PrimateAI
Benign
0.30
T
PROVEAN
Uncertain
-3.6
D;D
REVEL
Benign
0.14
Sift
Benign
0.082
T;T
Sift4G
Benign
0.17
T;T
Polyphen
0.0020
B;.
Vest4
0.15
MVP
0.23
MPC
0.14
ClinPred
0.050
T
GERP RS
1.9
Varity_R
0.15
gMVP
0.50

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs375331691; hg19: chr15-90226966; API