rs754629346
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM4BS2
The ENST00000371757.7(KCNT1):c.2061_2066del(p.Gly691_Gly692del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,476,612 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. G687G) has been classified as Likely benign.
Frequency
Consequence
ENST00000371757.7 inframe_deletion
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNT1 | NM_020822.3 | c.2061_2066del | p.Gly691_Gly692del | inframe_deletion | 19/31 | ENST00000371757.7 | NP_065873.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNT1 | ENST00000371757.7 | c.2061_2066del | p.Gly691_Gly692del | inframe_deletion | 19/31 | 1 | NM_020822.3 | ENSP00000360822 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152206Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000236 AC: 2AN: 84786Hom.: 0 AF XY: 0.0000227 AC XY: 1AN XY: 43998
GnomAD4 exome AF: 0.0000362 AC: 48AN: 1324406Hom.: 0 AF XY: 0.0000449 AC XY: 29AN XY: 645482
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152206Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74346
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 02, 2018 | See Variant Classification Assertion Criteria. - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2018 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Feb 06, 2024 | - - |
Developmental and epileptic encephalopathy, 14;C3554306:Autosomal dominant nocturnal frontal lobe epilepsy 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 01, 2023 | This variant, c.2061_2066del, results in the deletion of 2 amino acid(s) of the KCNT1 protein (p.Gly691_Gly692del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs754629346, gnomAD 0.007%). This variant has been observed in individual(s) with frontal lobe epilepsy (PMID: 32086284). ClinVar contains an entry for this variant (Variation ID: 473368). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
KCNT1-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 14, 2023 | The KCNT1 c.2061_2066del6 variant is predicted to result in an in-frame deletion (p.Gly691_Gly692del). This variant was reported in an individual with frontal lobe epilepsy (Krenn et al 2020. PubMed ID: 32086284). This variant is reported in 0.0092% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/9-138664610-CGGCGGT-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at