rs782040284
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001105206.3(LAMA4):c.3245C>T(p.Pro1082Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000178 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001105206.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LAMA4 | NM_001105206.3 | c.3245C>T | p.Pro1082Leu | missense_variant | Exon 24 of 39 | ENST00000230538.12 | NP_001098676.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LAMA4 | ENST00000230538.12 | c.3245C>T | p.Pro1082Leu | missense_variant | Exon 24 of 39 | 1 | NM_001105206.3 | ENSP00000230538.7 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251232Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135780
GnomAD4 exome AF: 0.0000178 AC: 26AN: 1461846Hom.: 0 Cov.: 31 AF XY: 0.0000234 AC XY: 17AN XY: 727232
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Dilated cardiomyopathy 1JJ Uncertain:1
This sequence change replaces proline with leucine at codon 1075 of the LAMA4 protein (p.Pro1075Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs782040284, ExAC 0.001%). This variant has not been reported in the literature in individuals affected with LAMA4-related conditions. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. -
not provided Uncertain:1
Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Reported in ClinVar but additional evidence is not available (ClinVar Variant ID #213594) -
Cardiovascular phenotype Uncertain:1
The p.P1075L variant (also known as c.3224C>T), located in coding exon 23 of the LAMA4 gene, results from a C to T substitution at nucleotide position 3224. The proline at codon 1075 is replaced by leucine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at