rs146609763
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_006059.4(LAMC3):c.538C>T(p.Arg180Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000202 in 1,613,620 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. R180R) has been classified as Likely benign.
Frequency
Consequence
NM_006059.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMC3 | NM_006059.4 | c.538C>T | p.Arg180Cys | missense_variant | 2/28 | ENST00000361069.9 | |
LAMC3 | XM_011518121.2 | c.538C>T | p.Arg180Cys | missense_variant | 2/28 | ||
LAMC3 | XM_006716921.3 | c.538C>T | p.Arg180Cys | missense_variant | 2/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMC3 | ENST00000361069.9 | c.538C>T | p.Arg180Cys | missense_variant | 2/28 | 2 | NM_006059.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000158 AC: 24AN: 152240Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000168 AC: 42AN: 250130Hom.: 1 AF XY: 0.000170 AC XY: 23AN XY: 135518
GnomAD4 exome AF: 0.000207 AC: 302AN: 1461262Hom.: 1 Cov.: 33 AF XY: 0.000235 AC XY: 171AN XY: 726970
GnomAD4 genome ? AF: 0.000158 AC: 24AN: 152358Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10AN XY: 74500
ClinVar
Submissions by phenotype
Occipital pachygyria and polymicrogyria Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Mar 25, 2019 | This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PP3. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 03, 2021 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2022 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 180 of the LAMC3 protein (p.Arg180Cys). This variant is present in population databases (rs146609763, gnomAD 0.03%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with LAMC3-related conditions. ClinVar contains an entry for this variant (Variation ID: 418860). 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 C15"). 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 specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 30, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at