1-156134954-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 10P and 5B. PVS1PM2BP6BS1
The NM_001406994.1(LMNA):c.125G>A(p.Trp42*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000719 in 1,614,198 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 Conflicting classifications of pathogenicity (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001406994.1 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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LMNA | NM_170707.4 | c.789G>A | p.Leu263Leu | synonymous_variant | Exon 4 of 12 | ENST00000368300.9 | NP_733821.1 | |
LMNA | NM_005572.4 | c.789G>A | p.Leu263Leu | synonymous_variant | Exon 4 of 10 | ENST00000677389.1 | NP_005563.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LMNA | ENST00000368300.9 | c.789G>A | p.Leu263Leu | synonymous_variant | Exon 4 of 12 | 1 | NM_170707.4 | ENSP00000357283.4 | ||
LMNA | ENST00000677389.1 | c.789G>A | p.Leu263Leu | synonymous_variant | Exon 4 of 10 | NM_005572.4 | ENSP00000503633.1 |
Frequencies
GnomAD3 genomes AF: 0.000440 AC: 67AN: 152216Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000875 AC: 22AN: 251396Hom.: 0 AF XY: 0.0000809 AC XY: 11AN XY: 135922
GnomAD4 exome AF: 0.0000335 AC: 49AN: 1461864Hom.: 0 Cov.: 33 AF XY: 0.0000275 AC XY: 20AN XY: 727232
GnomAD4 genome AF: 0.000440 AC: 67AN: 152334Hom.: 0 Cov.: 32 AF XY: 0.000416 AC XY: 31AN XY: 74494
ClinVar
Submissions by phenotype
not specified Benign:4
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This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
not provided Uncertain:1Benign:1
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Cardiomyopathy Benign:2
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Charcot-Marie-Tooth disease type 2 Benign:1
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Primary dilated cardiomyopathy Benign:1
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Cardiovascular phenotype Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at