rs760094343
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBP7
The NM_000334.4(SCN4A):c.240G>A(p.Leu80=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000437 in 1,600,740 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 (★). Synonymous variant affecting the same amino acid position (i.e. L80L) has been classified as Likely benign.
Frequency
Consequence
NM_000334.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN4A | NM_000334.4 | c.240G>A | p.Leu80= | synonymous_variant | 1/24 | ENST00000435607.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN4A | ENST00000435607.3 | c.240G>A | p.Leu80= | synonymous_variant | 1/24 | 1 | NM_000334.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152134Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000133 AC: 3AN: 225896Hom.: 0 AF XY: 0.00000818 AC XY: 1AN XY: 122324
GnomAD4 exome AF: 0.00000345 AC: 5AN: 1448606Hom.: 0 Cov.: 32 AF XY: 0.00000278 AC XY: 2AN XY: 719648
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152134Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74298
ClinVar
Submissions by phenotype
Hyperkalemic periodic paralysis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 07, 2017 | This sequence change affects codon 80 of the SCN4A mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the SCN4A protein. This variant is present in population databases (rs760094343, ExAC 0.003%). This variant has not been reported in the literature in individuals with SCN4A-related disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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