rs773444127
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong
The NM_032737.4(LMNB2):c.712G>A(p.Glu238Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000227 in 1,452,324 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E238V) has been classified as Uncertain significance.
Frequency
Consequence
NM_032737.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LMNB2 | NM_032737.4 | c.712G>A | p.Glu238Lys | missense_variant | 5/12 | ENST00000325327.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LMNB2 | ENST00000325327.4 | c.712G>A | p.Glu238Lys | missense_variant | 5/12 | 1 | NM_032737.4 | P1 | |
LMNB2 | ENST00000527409.1 | n.348G>A | non_coding_transcript_exon_variant | 2/4 | 5 | ||||
LMNB2 | ENST00000534495.1 | n.350G>A | non_coding_transcript_exon_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.0000211 AC: 5AN: 236526Hom.: 0 AF XY: 0.0000154 AC XY: 2AN XY: 129838
GnomAD4 exome AF: 0.0000227 AC: 33AN: 1452324Hom.: 0 Cov.: 39 AF XY: 0.0000166 AC XY: 12AN XY: 722858
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Lipodystrophy, partial, acquired, susceptibility to;C4225289:Progressive myoclonic epilepsy type 9 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 22, 2020 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with LMNB2-related disease. This variant is present in population databases (rs773444127, ExAC 0.003%). This sequence change replaces glutamic acid with lysine at codon 238 of the LMNB2 protein (p.Glu238Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at