rs145176060
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006059.4(LAMC3):c.557G>A(p.Arg186His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000496 in 1,613,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. R186R) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LAMC3 | NM_006059.4 | c.557G>A | p.Arg186His | missense_variant | 2/28 | ENST00000361069.9 | NP_006050.3 | |
LAMC3 | XM_011518121.2 | c.557G>A | p.Arg186His | missense_variant | 2/28 | XP_011516423.1 | ||
LAMC3 | XM_006716921.3 | c.557G>A | p.Arg186His | missense_variant | 2/23 | XP_006716984.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LAMC3 | ENST00000361069.9 | c.557G>A | p.Arg186His | missense_variant | 2/28 | 2 | NM_006059.4 | ENSP00000354360 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152234Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000721 AC: 18AN: 249776Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135412
GnomAD4 exome AF: 0.0000527 AC: 77AN: 1461154Hom.: 0 Cov.: 33 AF XY: 0.0000523 AC XY: 38AN XY: 726924
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152352Hom.: 0 Cov.: 33 AF XY: 0.0000268 AC XY: 2AN XY: 74514
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 21, 2021 | Reported in ClinVar as a variant of uncertain significance in trans with another missense variant in a patient with neurodevelopmental and neurological features as well as multiple congenital anomalies, but additional evidence is not available (ClinVar SCV000807630.1; Landrum et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25326635) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 01, 2022 | 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 561148). This missense change has been observed in individual(s) with clinical features of LAMC3-related conditions (PMID: 25326635). This variant is present in population databases (rs145176060, gnomAD 0.02%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 186 of the LAMC3 protein (p.Arg186His). - |
Occipital pachygyria and polymicrogyria Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 01, 2017 | Likely pathogenicity based on finding it once in our laboratory in trans with another missense variant in a 1-year-old female with global delays, spasticity, epilepsy, dysmorphisms, macrocephaly, obesity, feeding difficulties, structural brain anomalies (unspecified), hearing loss, vision loss, bicuspid aortic valve, nephromegaly, cleft palate - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at