rs765223466
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_198271.5(LMOD3):c.1139C>T(p.Pro380Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,613,510 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 (★). Synonymous variant affecting the same amino acid position (i.e. P380P) has been classified as Likely benign.
Frequency
Consequence
NM_198271.5 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 |
---|---|---|---|---|---|---|---|
LMOD3 | NM_198271.5 | c.1139C>T | p.Pro380Leu | missense_variant | 2/3 | ENST00000420581.7 | |
LMOD3 | NM_001304418.3 | c.1139C>T | p.Pro380Leu | missense_variant | 3/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LMOD3 | ENST00000420581.7 | c.1139C>T | p.Pro380Leu | missense_variant | 2/3 | 1 | NM_198271.5 | P1 | |
LMOD3 | ENST00000475434.1 | c.1139C>T | p.Pro380Leu | missense_variant | 3/4 | 5 | P1 | ||
LMOD3 | ENST00000489031.5 | c.1139C>T | p.Pro380Leu | missense_variant | 3/4 | 2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000198 AC: 3AN: 151822Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000161 AC: 4AN: 248950Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 135040
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461688Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4AN XY: 727126
GnomAD4 genome AF: 0.0000198 AC: 3AN: 151822Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74160
ClinVar
Submissions by phenotype
Nemaline myopathy 10 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 17, 2022 | This variant is present in population databases (rs765223466, gnomAD 0.006%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 380 of the LMOD3 protein (p.Pro380Leu). This variant has not been reported in the literature in individuals affected with LMOD3-related conditions. 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. ClinVar contains an entry for this variant (Variation ID: 475295). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at