rs753459417
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_198271.5(LMOD3):βc.450_455delβ(p.Glu150_Glu151del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.0000295 in 1,456,562 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β ). Synonymous variant affecting the same amino acid position (i.e. E150E) has been classified as Likely benign.
Frequency
Genomes: π 0.000053 ( 0 hom., cov: 31)
Exomes π: 0.000027 ( 0 hom. )
Consequence
LMOD3
NM_198271.5 inframe_deletion
NM_198271.5 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.69
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LMOD3 | NM_198271.5 | c.450_455del | p.Glu150_Glu151del | inframe_deletion | 2/3 | ENST00000420581.7 | |
LMOD3 | NM_001304418.3 | c.450_455del | p.Glu150_Glu151del | inframe_deletion | 3/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LMOD3 | ENST00000420581.7 | c.450_455del | p.Glu150_Glu151del | inframe_deletion | 2/3 | 1 | NM_198271.5 | P1 | |
LMOD3 | ENST00000475434.1 | c.450_455del | p.Glu150_Glu151del | inframe_deletion | 3/4 | 5 | P1 | ||
LMOD3 | ENST00000489031.5 | c.450_455del | p.Glu150_Glu151del | inframe_deletion | 3/4 | 2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000530 AC: 8AN: 151066Hom.: 0 Cov.: 31
GnomAD3 genomes
?
AF:
AC:
8
AN:
151066
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000303 AC: 5AN: 164826Hom.: 0 AF XY: 0.0000575 AC XY: 5AN XY: 86922
GnomAD3 exomes
AF:
AC:
5
AN:
164826
Hom.:
AF XY:
AC XY:
5
AN XY:
86922
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000268 AC: 35AN: 1305378Hom.: 0 AF XY: 0.0000339 AC XY: 22AN XY: 648622
GnomAD4 exome
AF:
AC:
35
AN:
1305378
Hom.:
AF XY:
AC XY:
22
AN XY:
648622
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000529 AC: 8AN: 151184Hom.: 0 Cov.: 31 AF XY: 0.0000813 AC XY: 6AN XY: 73822
GnomAD4 genome
?
AF:
AC:
8
AN:
151184
Hom.:
Cov.:
31
AF XY:
AC XY:
6
AN XY:
73822
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
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 | Invitae | Jun 25, 2022 | This variant, c.450_455del, results in the deletion of 2 amino acid(s) of the LMOD3 protein (p.Glu150_Glu151del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs753459417, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with LMOD3-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at