19-5711845-G-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The ENST00000360614.8(LONP1):c.796C>G(p.Leu266Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000241 in 1,612,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
ENST00000360614.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LONP1 | NM_004793.4 | c.796C>G | p.Leu266Val | missense_variant | 4/18 | ENST00000360614.8 | NP_004784.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LONP1 | ENST00000360614.8 | c.796C>G | p.Leu266Val | missense_variant | 4/18 | 1 | NM_004793.4 | ENSP00000353826 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 152186Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000104 AC: 26AN: 250000Hom.: 0 AF XY: 0.0000739 AC XY: 10AN XY: 135354
GnomAD4 exome AF: 0.000255 AC: 372AN: 1460564Hom.: 0 Cov.: 31 AF XY: 0.000252 AC XY: 183AN XY: 726690
GnomAD4 genome AF: 0.000112 AC: 17AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74336
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 05, 2024 | The c.796C>G (p.L266V) alteration is located in exon 4 (coding exon 4) of the LONP1 gene. This alteration results from a C to G substitution at nucleotide position 796, causing the leucine (L) at amino acid position 266 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
CODAS syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jan 12, 2017 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 10, 2024 | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 266 of the LONP1 protein (p.Leu266Val). This variant is present in population databases (rs373284466, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with LONP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 547905). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at