rs781802725
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PP3_StrongBS2
The NM_001105206.3(LAMA4):c.5380C>T(p.Arg1794Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000991 in 1,613,958 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1794S) has been classified as Uncertain significance.
Frequency
Consequence
NM_001105206.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA4 | NM_001105206.3 | c.5380C>T | p.Arg1794Cys | missense_variant | 39/39 | ENST00000230538.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA4 | ENST00000230538.12 | c.5380C>T | p.Arg1794Cys | missense_variant | 39/39 | 1 | NM_001105206.3 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152176Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251212Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135748
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461782Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727190
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152176Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74354
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 20, 2017 | The p.Arg1787Cys variant in LAMA4 has not been previously reported in individual s with cardiomyopathy, but has been identified in 1/16508 South Asian chromosome s by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbS NP rs781802725). Computational prediction tools and conservation analysis sugges t that the p.Arg1787Cys variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical si gnificance of the p.Arg1787Cys variant is uncertain. - |
Dilated cardiomyopathy 1JJ Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 03, 2021 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with LAMA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 505573). This variant is present in population databases (rs781802725, ExAC 0.006%). This sequence change replaces arginine with cysteine at codon 1787 of the LAMA4 protein (p.Arg1787Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at