rs786205280
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001105206.3(LAMA4):c.2912C>T(p.Ser971Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LAMA4 | NM_001105206.3 | c.2912C>T | p.Ser971Phe | missense_variant | Exon 22 of 39 | ENST00000230538.12 | NP_001098676.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LAMA4 | ENST00000230538.12 | c.2912C>T | p.Ser971Phe | missense_variant | Exon 22 of 39 | 1 | NM_001105206.3 | ENSP00000230538.7 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152150Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000518 AC: 13AN: 251128Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135720
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461766Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727186
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152150Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74308
ClinVar
Submissions by phenotype
Dilated cardiomyopathy 1JJ Uncertain:1
This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 964 of the LAMA4 protein (p.Ser964Phe). This variant is present in population databases (rs786205280, gnomAD 0.06%). 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: 191687). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests 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. -
not provided Uncertain:1
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Cardiovascular phenotype Uncertain:1
The p.S964F variant (also known as c.2891C>T), located in coding exon 21 of the LAMA4 gene, results from a C to T substitution at nucleotide position 2891. The serine at codon 964 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at