3-69109096-T-TA
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_198271.5(LMOD3):c.1681_1682insT(p.Ter561LeufsTer8) variant causes a frameshift, stop lost change. The variant allele was found at a frequency of 0.00000207 in 1,448,518 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
LMOD3
NM_198271.5 frameshift, stop_lost
NM_198271.5 frameshift, stop_lost
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.34
Genes affected
LMOD3 (HGNC:6649): (leiomodin 3) The protein encoded by this gene is a member of the leiomodin family of proteins. This protein contains three actin-binding domains, a tropomyosin domain, a leucine-rich repeat domain, and a Wiskott-Aldrich syndrome protein homology 2 domain (WH2). Localization of this protein to the pointed ends of thin filaments has been observed, and there is evidence that this protein acts as a catalyst of actin nucleation, and is important to the organization of sarcomeric thin filaments in skeletal muscles. Mutations in this gene have been associated as one cause of Nemaline myopathy, as other genes have also been linked to this disorder. Nemaline myopathy is a disorder characterized by nonprogressive generalized muscle weakness and protein inclusions (nemaline bodies) in skeletal myofibers. Patients with mutations in this gene often present with a severe congenital form of the disorder. [provided by RefSeq, Jan 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Stoplost variant in NM_198271.5 Downstream stopcodon found after 63 codons.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LMOD3 | NM_198271.5 | c.1681_1682insT | p.Ter561LeufsTer8 | frameshift_variant, stop_lost | 3/3 | ENST00000420581.7 | NP_938012.2 | |
LMOD3 | NM_001304418.3 | c.1681_1682insT | p.Ter561LeufsTer8 | frameshift_variant, stop_lost | 4/4 | NP_001291347.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LMOD3 | ENST00000420581.7 | c.1681_1682insT | p.Ter561LeufsTer8 | frameshift_variant, stop_lost | 3/3 | 1 | NM_198271.5 | ENSP00000414670 | P1 | |
LMOD3 | ENST00000475434.1 | c.1681_1682insT | p.Ter561LeufsTer8 | frameshift_variant, stop_lost | 4/4 | 5 | ENSP00000418645 | P1 | ||
LMOD3 | ENST00000489031.5 | c.1681_1682insT | p.Ter561LeufsTer8 | frameshift_variant, stop_lost | 4/4 | 2 | ENSP00000417210 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000207 AC: 3AN: 1448518Hom.: 0 Cov.: 29 AF XY: 0.00000417 AC XY: 3AN XY: 719032
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29
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3
AN XY:
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Nemaline myopathy 10 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 18, 2018 | 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. This variant has not been reported in the literature in individuals with LMOD3-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change disrupts the translational stop signal of the LMOD3 mRNA. It is expected to extend the length of the LMOD3 protein by 7 additional amino acid residues. - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at