rs775901528
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PP2PP3_Moderate
The NM_005097.4(LGI1):c.1331T>A(p.Val444Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,614,074 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. V444M) has been classified as Uncertain significance.
Frequency
Consequence
NM_005097.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LGI1 | NM_005097.4 | c.1331T>A | p.Val444Glu | missense_variant | 8/8 | ENST00000371418.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LGI1 | ENST00000371418.9 | c.1331T>A | p.Val444Glu | missense_variant | 8/8 | 1 | NM_005097.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152198Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251194Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135730
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461876Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727238
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152198Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74352
ClinVar
Submissions by phenotype
Autosomal dominant epilepsy with auditory features Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 11, 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C35"). ClinVar contains an entry for this variant (Variation ID: 571992). This variant has not been reported in the literature in individuals affected with LGI1-related conditions. This variant is present in population databases (rs775901528, gnomAD 0.0009%). This sequence change replaces valine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 444 of the LGI1 protein (p.Val444Glu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at