rs1057520165
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_006059.4(LAMC3):c.42_50dupACCGCGGGC(p.Ala17_Ala18insProArgAla) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000299 in 1,293,078 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00013 ( 1 hom. )
Consequence
LAMC3
NM_006059.4 disruptive_inframe_insertion
NM_006059.4 disruptive_inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.29
Genes affected
LAMC3 (HGNC:6494): (laminin subunit gamma 3) Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Laminins are composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively) and they form a cruciform structure consisting of 3 short arms, each formed by a different chain, and a long arm composed of all 3 chains. Each laminin chain is a multidomain protein encoded by a distinct gene. Several isoforms of each chain have been described. Different alpha, beta and gamma chain isomers combine to give rise to different heterotrimeric laminin isoforms which are designated by Arabic numerals in the order of their discovery, i.e. alpha1beta1gamma1 heterotrimer is laminin 1. The biological functions of the different chains and trimer molecules are largely unknown, but some of the chains have been shown to differ with respect to their tissue distribution, presumably reflecting diverse functions in vivo. This gene encodes the gamma chain isoform laminin, gamma 3. The gamma 3 chain is most similar to the gamma 1 chain, and contains all the 6 domains expected of the gamma chain. It is a component of laminin 12. The gamma 3 chain is broadly expressed in skin, heart, lung, and the reproductive tracts. In skin, it is seen within the basement membrane of the dermal-epidermal junction at points of nerve penetration. Gamma 3 is also a prominent element of the apical surface of ciliated epithelial cells of lung, oviduct, epididymis, ductus deferens, and seminiferous tubules. The distribution of gamma 3-containing laminins along ciliated epithelial surfaces suggests that the apical laminins are important in the morphogenesis and structural stability of the ciliated processes of these cells. [provided by RefSeq, Aug 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_006059.4.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| LAMC3 | NM_006059.4 | c.42_50dupACCGCGGGC | p.Ala17_Ala18insProArgAla | disruptive_inframe_insertion | Exon 1 of 28 | ENST00000361069.9 | NP_006050.3 | |
| LAMC3 | XM_011518121.2 | c.42_50dupACCGCGGGC | p.Ala17_Ala18insProArgAla | disruptive_inframe_insertion | Exon 1 of 28 | XP_011516423.1 | ||
| LAMC3 | XM_006716921.3 | c.42_50dupACCGCGGGC | p.Ala17_Ala18insProArgAla | disruptive_inframe_insertion | Exon 1 of 23 | XP_006716984.1 |
Ensembl
Frequencies
GnomAD3 genomes 0.00156 AC: 236AN: 151236Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.000130 AC: 148AN: 1141734Hom.: 1 Cov.: 29 AF XY: 0.000118 AC XY: 65AN XY: 550962
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GnomAD4 genome 0.00157 AC: 238AN: 151344Hom.: 0 Cov.: 32 AF XY: 0.00157 AC XY: 116AN XY: 73934
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:3Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:2Benign:1
Jan 21, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Sep 13, 2016
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Jun 30, 2022
GeneDx
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
In-frame insertion of 3 amino acids in a non-repeat region; Has not been previously published as pathogenic or benign to our knowledge -
Occipital pachygyria and polymicrogyria Uncertain:1
Oct 11, 2019
New York Genome Center
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at