rs576711704
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001105206.3(LAMA4):c.997G>T(p.Ala333Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,612,564 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 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. A333T) has been classified as Likely benign.
Frequency
Consequence
NM_001105206.3 missense
Scores
Clinical Significance
Conservation
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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.997G>T | p.Ala333Ser | missense_variant | 9/39 | ENST00000230538.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA4 | ENST00000230538.12 | c.997G>T | p.Ala333Ser | missense_variant | 9/39 | 1 | NM_001105206.3 | A1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152088Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251368Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135852
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1460476Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726670
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152088Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74276
ClinVar
Submissions by phenotype
Dilated cardiomyopathy 1JJ Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 27, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 326 of the LAMA4 protein (p.Ala326Ser). This variant is present in population databases (rs576711704, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with LAMA4-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at