rs200440843
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4_ModerateBP6
The NM_001161352.2(KCNMA1):c.2675C>T(p.Thr892Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000075 in 1,613,896 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T892T) has been classified as Likely benign.
Frequency
Consequence
NM_001161352.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNMA1 | NM_001161352.2 | c.2675C>T | p.Thr892Met | missense_variant | 22/28 | ENST00000286628.14 | |
LOC124902466 | XR_007062207.1 | n.591G>A | non_coding_transcript_exon_variant | 3/3 | |||
KCNMA1-AS1 | NR_120655.1 | n.458-28434G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNMA1 | ENST00000286628.14 | c.2675C>T | p.Thr892Met | missense_variant | 22/28 | 1 | NM_001161352.2 | A2 | |
KCNMA1-AS1 | ENST00000458661.6 | n.426-28434G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152166Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000135 AC: 34AN: 251326Hom.: 1 AF XY: 0.000169 AC XY: 23AN XY: 135820
GnomAD4 exome AF: 0.0000794 AC: 116AN: 1461730Hom.: 1 Cov.: 31 AF XY: 0.000103 AC XY: 75AN XY: 727192
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152166Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74326
ClinVar
Submissions by phenotype
Generalized epilepsy-paroxysmal dyskinesia syndrome Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 09, 2016 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 08, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at