chr19-5692065-G-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_004793.4(LONP1):āc.2847C>Gā(p.Asp949Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000311 in 1,607,704 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 (ā ). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin ClinVar.
Frequency
Consequence
NM_004793.4 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 | UniProt |
---|---|---|---|---|---|---|---|
LONP1 | NM_004793.4 | c.2847C>G | p.Asp949Glu | missense_variant | 18/18 | ENST00000360614.8 | |
LONP1 | NM_001276479.2 | c.2655C>G | p.Asp885Glu | missense_variant | 19/19 | ||
LONP1 | NM_001276480.1 | c.2259C>G | p.Asp753Glu | missense_variant | 18/18 | ||
LONP1 | NR_076392.2 | n.2652C>G | non_coding_transcript_exon_variant | 19/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LONP1 | ENST00000360614.8 | c.2847C>G | p.Asp949Glu | missense_variant | 18/18 | 1 | NM_004793.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000672 AC: 1AN: 148918Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1458786Hom.: 0 Cov.: 34 AF XY: 0.00000551 AC XY: 4AN XY: 725474
GnomAD4 genome AF: 0.00000672 AC: 1AN: 148918Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 72620
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 31, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 1470312). This variant has not been reported in the literature in individuals affected with LONP1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 949 of the LONP1 protein (p.Asp949Glu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at