NM_006059.4:c.236C>T
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.
The NM_006059.4(LAMC3):c.236C>T(p.Ala79Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000205 in 1,547,042 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_006059.4 missense
Scores
Clinical Significance
Conservation
Publications
- occipital pachygyria and polymicrogyriaInheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Orphanet, Illumina
- complex neurodevelopmental disorderInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
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ACMG classification
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LAMC3 | NM_006059.4 | c.236C>T | p.Ala79Val | missense_variant | Exon 1 of 28 | ENST00000361069.9 | NP_006050.3 | |
LAMC3 | XM_011518121.2 | c.236C>T | p.Ala79Val | missense_variant | Exon 1 of 28 | XP_011516423.1 | ||
LAMC3 | XM_006716921.3 | c.236C>T | p.Ala79Val | missense_variant | Exon 1 of 23 | XP_006716984.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152182Hom.: 0 Cov.: 31 show subpopulations
GnomAD2 exomes AF: 0.0000899 AC: 13AN: 144672 AF XY: 0.0000900 show subpopulations
GnomAD4 exome AF: 0.000214 AC: 299AN: 1394860Hom.: 0 Cov.: 33 AF XY: 0.000180 AC XY: 124AN XY: 688162 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.000118 AC: 18AN: 152182Hom.: 0 Cov.: 31 AF XY: 0.000108 AC XY: 8AN XY: 74332 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not provided Uncertain:3
- -
In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 79 of the LAMC3 protein (p.Ala79Val). This variant is present in population databases (rs772194826, gnomAD 0.02%). 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: 376996). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. -
Inborn genetic diseases Uncertain:1
The c.236C>T (p.A79V) alteration is located in exon 1 (coding exon 1) of the LAMC3 gene. This alteration results from a C to T substitution at nucleotide position 236, causing the alanine (A) at amino acid position 79 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at