chr16-48261436-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_031490.5(LONP2):c.736C>T(p.Arg246Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000995 in 1,597,504 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00010 ( 0 hom. )
Consequence
LONP2
NM_031490.5 missense
NM_031490.5 missense
Scores
2
11
6
Clinical Significance
Conservation
PhyloP100: 4.03
Genes affected
LONP2 (HGNC:20598): (lon peptidase 2, peroxisomal) In human, peroxisomes function primarily to catalyze fatty acid beta-oxidation and, as a by-product, produce hydrogen peroxide and superoxide. The protein encoded by this gene is an ATP-dependent protease that likely plays a role in maintaining overall peroxisome homeostasis as well as proteolytically degrading peroxisomal proteins damaged by oxidation. The protein has an N-terminal Lon N substrate recognition domain, an ATPase domain, a proteolytic domain, and, in some isoforms, a C-terminal peroxisome targeting sequence. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jan 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LONP2 | NM_031490.5 | c.736C>T | p.Arg246Cys | missense_variant | 5/15 | ENST00000285737.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LONP2 | ENST00000285737.9 | c.736C>T | p.Arg246Cys | missense_variant | 5/15 | 1 | NM_031490.5 | P1 | |
LONP2 | ENST00000535754.5 | c.604C>T | p.Arg202Cys | missense_variant | 4/14 | 1 | |||
LONP2 | ENST00000416006.7 | c.604C>T | p.Arg202Cys | missense_variant, NMD_transcript_variant | 4/13 | 2 | |||
LONP2 | ENST00000566755.5 | c.736C>T | p.Arg246Cys | missense_variant, NMD_transcript_variant | 5/14 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000793 AC: 12AN: 151400Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000137 AC: 33AN: 241290Hom.: 0 AF XY: 0.000161 AC XY: 21AN XY: 130774
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GnomAD4 exome AF: 0.000102 AC: 147AN: 1446104Hom.: 0 Cov.: 29 AF XY: 0.000100 AC XY: 72AN XY: 719476
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GnomAD4 genome ? AF: 0.0000793 AC: 12AN: 151400Hom.: 0 Cov.: 32 AF XY: 0.0000677 AC XY: 5AN XY: 73858
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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 | Apr 08, 2022 | The c.736C>T (p.R246C) alteration is located in exon 5 (coding exon 5) of the LONP2 gene. This alteration results from a C to T substitution at nucleotide position 736, causing the arginine (R) at amino acid position 246 to be replaced by a cysteine (C). 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
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MutPred
Loss of MoRF binding (P = 0.0012);.;
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Calibrated prediction
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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