chr1-156115148-T-G
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PP2PP3_Moderate
The NM_170707.4(LMNA):c.230T>G(p.Ile77Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. I77T) has been classified as Uncertain significance.
Frequency
Consequence
NM_170707.4 missense
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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LMNA | NM_170707.4 | c.230T>G | p.Ile77Ser | missense_variant | 1/12 | ENST00000368300.9 | |
LMNA | NM_005572.4 | c.230T>G | p.Ile77Ser | missense_variant | 1/10 | ENST00000677389.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LMNA | ENST00000368300.9 | c.230T>G | p.Ile77Ser | missense_variant | 1/12 | 1 | NM_170707.4 | P1 | |
LMNA | ENST00000677389.1 | c.230T>G | p.Ile77Ser | missense_variant | 1/10 | NM_005572.4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease type 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 20, 2019 | 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 LMNA-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with serine at codon 77 of the LMNA protein (p.Ile77Ser). The isoleucine residue is highly conserved and there is a large physicochemical difference between isoleucine and serine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at