rs1271772498
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_004793.4(LONP1):c.2848G>T(p.Glu950*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,540 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 (no stars). Synonymous variant affecting the same amino acid position (i.e. E950E) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
LONP1
NM_004793.4 stop_gained
NM_004793.4 stop_gained
Scores
2
5
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.29
Publications
0 publications found
Genes affected
LONP1 (HGNC:9479): (lon peptidase 1, mitochondrial) This gene encodes a mitochondrial matrix protein that belongs to the Lon family of ATP-dependent proteases. This protein mediates the selective degradation of misfolded, unassembled or oxidatively damaged polypeptides in the mitochondrial matrix. It may also have a chaperone function in the assembly of inner membrane protein complexes, and participate in the regulation of mitochondrial gene expression and maintenance of the integrity of the mitochondrial genome. Decreased expression of this gene has been noted in a patient with hereditary spastic paraplegia (PMID:18378094). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Feb 2013]
RPL36 (HGNC:13631): (ribosomal protein L36) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L36E family of ribosomal proteins. It is located in the cytoplasm. Transcript variants derived from alternative splicing exist; they encode the same protein. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0111 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_004793.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| LONP1 | MANE Select | c.2848G>T | p.Glu950* | stop_gained | Exon 18 of 18 | NP_004784.2 | |||
| LONP1 | c.2656G>T | p.Glu886* | stop_gained | Exon 19 of 19 | NP_001263408.1 | P36776-2 | |||
| LONP1 | c.2260G>T | p.Glu754* | stop_gained | Exon 18 of 18 | NP_001263409.1 | P36776-3 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| LONP1 | TSL:1 MANE Select | c.2848G>T | p.Glu950* | stop_gained | Exon 18 of 18 | ENSP00000353826.2 | P36776-1 | ||
| LONP1 | TSL:1 | c.2458G>T | p.Glu820* | stop_gained | Exon 18 of 18 | ENSP00000465139.1 | K7EJE8 | ||
| LONP1 | c.3034G>T | p.Glu1012* | stop_gained | Exon 19 of 19 | ENSP00000628541.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461540Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1AN XY: 727062 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461540
Hom.:
Cov.:
34
AF XY:
AC XY:
1
AN XY:
727062
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33478
American (AMR)
AF:
AC:
0
AN:
44700
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26118
East Asian (EAS)
AF:
AC:
0
AN:
39698
South Asian (SAS)
AF:
AC:
0
AN:
86238
European-Finnish (FIN)
AF:
AC:
0
AN:
53312
Middle Eastern (MID)
AF:
AC:
0
AN:
5762
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111844
Other (OTH)
AF:
AC:
0
AN:
60390
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.675
Heterozygous variant carriers
0
0
1
1
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2
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0.60
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
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<30
30-35
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
PhyloP100
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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