rs59564495
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PM4_SupportingPP5_Moderate
The NM_001406994.1(LMNA):c.193_195delGGG(p.Gly65del) variant causes a conservative inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. G65G) has been classified as Uncertain significance.
Frequency
Consequence
NM_001406994.1 conservative_inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LMNA | NM_170707.4 | c.857_859delGGG | p.Gly286del | disruptive_inframe_deletion | Exon 5 of 12 | ENST00000368300.9 | NP_733821.1 | |
LMNA | NM_005572.4 | c.857_859delGGG | p.Gly286del | disruptive_inframe_deletion | Exon 5 of 10 | ENST00000677389.1 | NP_005563.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LMNA | ENST00000368300.9 | c.857_859delGGG | p.Gly286del | disruptive_inframe_deletion | Exon 5 of 12 | 1 | NM_170707.4 | ENSP00000357283.4 | ||
LMNA | ENST00000677389.1 | c.857_859delGGG | p.Gly286del | disruptive_inframe_deletion | Exon 5 of 10 | NM_005572.4 | ENSP00000503633.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease type 2 Pathogenic:1
This variant, c.857_859delGGG, results in the deletion of 1 amino acid(s) of the LMNA protein (p.Gly286del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with cardiomyopathy (Invitae). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at