rs560898148
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Benign. The variant received -11 ACMG points: 1P and 12B. PM4_SupportingBP6_Very_StrongBS2
The NM_004793.4(LONP1):c.730_732delAAG(p.Lys244del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.000614 in 1,613,192 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. K244K) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.0035 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00032 ( 2 hom. )
Consequence
LONP1
NM_004793.4 conservative_inframe_deletion
NM_004793.4 conservative_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.73
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]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -11 ACMG points.
PM4
Nonframeshift variant in NON repetitive region in NM_004793.4. Strenght limited to Supporting due to length of the change: 1aa.
BP6
Variant 19-5711908-CCTT-C is Benign according to our data. Variant chr19-5711908-CCTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 445759.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-5711908-CCTT-C is described in Lovd as [Benign].
BS2
High Homozygotes in GnomAd4 at 2 AR,XL gene
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.00346 AC: 527AN: 152192Hom.: 2 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
527
AN:
152192
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.000886 AC: 222AN: 250704 AF XY: 0.000811 show subpopulations
GnomAD2 exomes
AF:
AC:
222
AN:
250704
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000317 AC: 463AN: 1460882Hom.: 2 AF XY: 0.000308 AC XY: 224AN XY: 726832 show subpopulations
GnomAD4 exome
AF:
AC:
463
AN:
1460882
Hom.:
AF XY:
AC XY:
224
AN XY:
726832
show subpopulations
African (AFR)
AF:
AC:
390
AN:
33474
American (AMR)
AF:
AC:
25
AN:
44718
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26116
East Asian (EAS)
AF:
AC:
0
AN:
39694
South Asian (SAS)
AF:
AC:
2
AN:
86254
European-Finnish (FIN)
AF:
AC:
0
AN:
52738
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
8
AN:
1111736
Other (OTH)
AF:
AC:
38
AN:
60384
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.468
Heterozygous variant carriers
0
27
54
81
108
135
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00347 AC: 528AN: 152310Hom.: 2 Cov.: 32 AF XY: 0.00334 AC XY: 249AN XY: 74460 show subpopulations
GnomAD4 genome
AF:
AC:
528
AN:
152310
Hom.:
Cov.:
32
AF XY:
AC XY:
249
AN XY:
74460
show subpopulations
African (AFR)
AF:
AC:
509
AN:
41578
American (AMR)
AF:
AC:
14
AN:
15306
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5150
South Asian (SAS)
AF:
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
AC:
0
AN:
10630
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68024
Other (OTH)
AF:
AC:
4
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.514
Heterozygous variant carriers
0
27
54
80
107
134
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Jan 30, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Apr 24, 2017
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Apr 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
LONP1: PM4:Supporting, BS1, BS2 -
LONP1-related disorder Benign:1
Oct 03, 2022
PreventionGenetics, part of Exact Sciences
Significance:Benign
Review Status:no assertion criteria provided
Collection Method:clinical testing
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
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
Loading publications...