rs138481447
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_006059.4(LAMC3):āc.3674T>Cā(p.Val1225Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,613,992 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_006059.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMC3 | NM_006059.4 | c.3674T>C | p.Val1225Ala | missense_variant | 22/28 | ENST00000361069.9 | |
LAMC3 | XM_011518121.2 | c.3674T>C | p.Val1225Ala | missense_variant | 22/28 | ||
LAMC3 | XM_006716921.3 | c.3674T>C | p.Val1225Ala | missense_variant | 22/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMC3 | ENST00000361069.9 | c.3674T>C | p.Val1225Ala | missense_variant | 22/28 | 2 | NM_006059.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000637 AC: 97AN: 152188Hom.: 1 Cov.: 31
GnomAD3 exomes AF: 0.000545 AC: 137AN: 251156Hom.: 0 AF XY: 0.000471 AC XY: 64AN XY: 135864
GnomAD4 exome AF: 0.00111 AC: 1626AN: 1461686Hom.: 2 Cov.: 31 AF XY: 0.00111 AC XY: 804AN XY: 727180
GnomAD4 genome ? AF: 0.000637 AC: 97AN: 152306Hom.: 1 Cov.: 31 AF XY: 0.000617 AC XY: 46AN XY: 74494
ClinVar
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | LAMC3: BP4 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 13, 2021 | 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 - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 15, 2022 | The c.3674T>C (p.V1225A) alteration is located in exon 22 (coding exon 22) of the LAMC3 gene. This alteration results from a T to C substitution at nucleotide position 3674, causing the valine (V) at amino acid position 1225 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Occipital pachygyria and polymicrogyria Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
LAMC3-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 21, 2023 | The LAMC3 c.3674T>C variant is predicted to result in the amino acid substitution p.Val1225Ala. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.10% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/9-133952618-T-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at