rs141758463
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_006059.4(LAMC3):āc.290A>Gā(p.Gln97Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000497 in 1,552,310 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_006059.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LAMC3 | NM_006059.4 | c.290A>G | p.Gln97Arg | missense_variant | 1/28 | ENST00000361069.9 | NP_006050.3 | |
LAMC3 | XM_011518121.2 | c.290A>G | p.Gln97Arg | missense_variant | 1/28 | XP_011516423.1 | ||
LAMC3 | XM_006716921.3 | c.290A>G | p.Gln97Arg | missense_variant | 1/23 | XP_006716984.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LAMC3 | ENST00000361069.9 | c.290A>G | p.Gln97Arg | missense_variant | 1/28 | 2 | NM_006059.4 | ENSP00000354360 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000342 AC: 52AN: 152168Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000501 AC: 77AN: 153754Hom.: 0 AF XY: 0.000657 AC XY: 54AN XY: 82200
GnomAD4 exome AF: 0.000514 AC: 720AN: 1400024Hom.: 2 Cov.: 33 AF XY: 0.000562 AC XY: 388AN XY: 690800
GnomAD4 genome AF: 0.000341 AC: 52AN: 152286Hom.: 0 Cov.: 31 AF XY: 0.000322 AC XY: 24AN XY: 74464
ClinVar
Submissions by phenotype
not provided Uncertain:3Benign:3
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 04, 2023 | 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 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 25, 2022 | This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 97 of the LAMC3 protein (p.Gln97Arg). This variant is present in population databases (rs141758463, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. 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: 279830). 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: "Possibly 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. - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Occipital pachygyria and polymicrogyria Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at