10-76949303-C-T
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2
The NM_001161352.2(KCNMA1):c.2548G>A(p.Val850Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000324 in 1,614,042 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. V850V) has been classified as Likely benign.
Frequency
Consequence
NM_001161352.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNMA1 | NM_001161352.2 | c.2548G>A | p.Val850Ile | missense_variant | 22/28 | ENST00000286628.14 | |
LOC124902466 | XR_007062207.1 | n.718C>T | non_coding_transcript_exon_variant | 3/3 | |||
KCNMA1-AS1 | NR_120655.1 | n.458-28307C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNMA1 | ENST00000286628.14 | c.2548G>A | p.Val850Ile | missense_variant | 22/28 | 1 | NM_001161352.2 | A2 | |
KCNMA1-AS1 | ENST00000458661.6 | n.426-28307C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000283 AC: 43AN: 152060Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000577 AC: 145AN: 251132Hom.: 3 AF XY: 0.000855 AC XY: 116AN XY: 135748
GnomAD4 exome AF: 0.000329 AC: 481AN: 1461864Hom.: 5 Cov.: 31 AF XY: 0.000470 AC XY: 342AN XY: 727232
GnomAD4 genome ? AF: 0.000276 AC: 42AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.000323 AC XY: 24AN XY: 74390
ClinVar
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | KCNMA1: PP2, BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 19, 2020 | - - |
Generalized epilepsy-paroxysmal dyskinesia syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 25, 2018 | - - |
KCNMA1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 02, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at