rs782192817
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001105206.3(LAMA4):c.153C>A(p.Ser51Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000145 in 1,586,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S51T) has been classified as Uncertain significance.
Frequency
Consequence
NM_001105206.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA4 | NM_001105206.3 | c.153C>A | p.Ser51Arg | missense_variant | 2/39 | ENST00000230538.12 | |
LAMA4-AS1 | NR_121193.1 | n.181+17082G>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA4 | ENST00000230538.12 | c.153C>A | p.Ser51Arg | missense_variant | 2/39 | 1 | NM_001105206.3 | A1 | |
LAMA4-AS1 | ENST00000433684.6 | n.684+17082G>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152236Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000151 AC: 3AN: 198640Hom.: 0 AF XY: 0.0000187 AC XY: 2AN XY: 107012
GnomAD4 exome AF: 0.0000146 AC: 21AN: 1433840Hom.: 0 Cov.: 31 AF XY: 0.0000155 AC XY: 11AN XY: 710880
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152236Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74378
ClinVar
Submissions by phenotype
Dilated cardiomyopathy 1JJ Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 21, 2023 | This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 51 of the LAMA4 protein (p.Ser51Arg). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 406145). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 09, 2021 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Oct 11, 2023 | Variant summary: LAMA4 c.153C>A (p.Ser51Arg) results in a non-conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.5e-05 in 198640 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.153C>A in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 30, 2023 | The p.S51R variant (also known as c.153C>A), located in coding exon 1 of the LAMA4 gene, results from a C to A substitution at nucleotide position 153. The serine at codon 51 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at