3-69109117-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_198271.5(LMOD3):c.1661A>G(p.Gln554Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_198271.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LMOD3 | ENST00000420581.7 | c.1661A>G | p.Gln554Arg | missense_variant | Exon 3 of 3 | 1 | NM_198271.5 | ENSP00000414670.3 | ||
LMOD3 | ENST00000475434.1 | c.1661A>G | p.Gln554Arg | missense_variant | Exon 4 of 4 | 5 | ENSP00000418645.1 | |||
LMOD3 | ENST00000489031.5 | c.1661A>G | p.Gln554Arg | missense_variant | Exon 4 of 4 | 2 | ENSP00000417210.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 29
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Nemaline myopathy 10 Uncertain:1
This sequence change replaces glutamine with arginine at codon 554 of the LMOD3 protein (p.Gln554Arg). The glutamine residue is weakly conserved and there is a small physicochemical difference between glutamine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with LMOD3-related conditions. 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at