6-112119191-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001105206.3(LAMA4):c.4786G>A(p.Gly1596Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. G1596G) has been classified as Likely benign.
Frequency
Consequence
NM_001105206.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA4 | NM_001105206.3 | c.4786G>A | p.Gly1596Ser | missense_variant | 34/39 | ENST00000230538.12 | |
LOC107986633 | XR_001744299.2 | n.439+2764C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA4 | ENST00000230538.12 | c.4786G>A | p.Gly1596Ser | missense_variant | 34/39 | 1 | NM_001105206.3 | A1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251146Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135726
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461750Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727188
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Dilated cardiomyopathy 1JJ Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 05, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1589 of the LAMA4 protein (p.Gly1589Ser). This variant is present in population databases (rs373949918, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with LAMA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 579669). 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: "Deleterious"; PolyPhen-2: "Probably 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | AiLife Diagnostics, AiLife Diagnostics | Dec 30, 2021 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 22, 2023 | The c.4765G>A (p.G1589S) alteration is located in exon 34 (coding exon 33) of the LAMA4 gene. This alteration results from a G to A substitution at nucleotide position 4765, causing the glycine (G) at amino acid position 1589 to be replaced by a serine (S). 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