rs1397556923
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3_Moderate
The NM_001161352.2(KCNMA1):c.3416G>A(p.Arg1139Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,874 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1139W) has been classified as Uncertain significance.
Frequency
Consequence
NM_001161352.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNMA1 | NM_001161352.2 | c.3416G>A | p.Arg1139Gln | missense_variant | 27/28 | ENST00000286628.14 | |
KCNMA1-AS1 | NR_120655.1 | n.238+1215C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNMA1 | ENST00000286628.14 | c.3416G>A | p.Arg1139Gln | missense_variant | 27/28 | 1 | NM_001161352.2 | A2 | |
KCNMA1-AS1 | ENST00000458661.6 | n.206+1215C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152064Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461810Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727216
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152064Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74268
ClinVar
Submissions by phenotype
Generalized epilepsy-paroxysmal dyskinesia syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 04, 2017 | 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. 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. This variant has not been reported in the literature in individuals with KCNMA1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with glutamine at codon 1081 of the KCNMA1 protein (p.Arg1081Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at