rs987482450
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PM1PM2PP2BP4
The ENST00000368300.9(LMNA):c.352G>T(p.Ala118Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,453,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. A118G) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000368300.9 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LMNA | NM_170707.4 | c.352G>T | p.Ala118Ser | missense_variant | 1/12 | ENST00000368300.9 | NP_733821.1 | |
LMNA | NM_005572.4 | c.352G>T | p.Ala118Ser | missense_variant | 1/10 | ENST00000677389.1 | NP_005563.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LMNA | ENST00000368300.9 | c.352G>T | p.Ala118Ser | missense_variant | 1/12 | 1 | NM_170707.4 | ENSP00000357283 | P1 | |
LMNA | ENST00000677389.1 | c.352G>T | p.Ala118Ser | missense_variant | 1/10 | NM_005572.4 | ENSP00000503633 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000138 AC: 2AN: 1453038Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 2AN XY: 722860
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease type 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 31, 2021 | This sequence change replaces alanine with serine at codon 118 of the LMNA protein (p.Ala118Ser). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with LMNA-related conditions. 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 C65"). 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. - |
LMNA-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | May 24, 2024 | The LMNA c.352G>T variant is predicted to result in the amino acid substitution p.Ala118Ser. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at