rs1391693620
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Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PM4_Supporting
The NM_001165963.4(SCN1A):c.1651_1653delTCC(p.Ser551del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.00000657 in 152,128 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Consequence
SCN1A
NM_001165963.4 conservative_inframe_deletion
NM_001165963.4 conservative_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.64
Genes affected
SCN1A (HGNC:10585): (sodium voltage-gated channel alpha subunit 1) Voltage-dependent sodium channels are heteromeric complexes that regulate sodium exchange between intracellular and extracellular spaces and are essential for the generation and propagation of action potentials in muscle cells and neurons. Each sodium channel is composed of a large pore-forming, glycosylated alpha subunit and two smaller beta subunits. This gene encodes a sodium channel alpha subunit, which has four homologous domains, each of which contains six transmembrane regions. Allelic variants of this gene are associated with generalized epilepsy with febrile seizures and epileptic encephalopathy. Alternative splicing results in multiple transcript variants. The RefSeq Project has decided to create four representative RefSeq records. Three of the transcript variants are supported by experimental evidence and the fourth contains alternate 5' untranslated exons, the exact combination of which have not been experimentally confirmed for the full-length transcript. [provided by RefSeq, Oct 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM1
In a modified_residue Phosphoserine (size 0) in uniprot entity SCN1A_HUMAN
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_001165963.4. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SCN1A | NM_001165963.4 | c.1651_1653delTCC | p.Ser551del | conservative_inframe_deletion | 13/29 | ENST00000674923.1 | NP_001159435.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCN1A | ENST00000674923.1 | c.1651_1653delTCC | p.Ser551del | conservative_inframe_deletion | 13/29 | NM_001165963.4 | ENSP00000501589.1 | |||
SCN1A | ENST00000303395.9 | c.1651_1653delTCC | p.Ser551del | conservative_inframe_deletion | 12/28 | 5 | ENSP00000303540.4 | |||
SCN1A | ENST00000375405.7 | c.1651_1653delTCC | p.Ser551del | conservative_inframe_deletion | 10/26 | 5 | ENSP00000364554.3 | |||
SCN1A | ENST00000409050.1 | c.1651_1653delTCC | p.Ser551del | conservative_inframe_deletion | 10/26 | 5 | ENSP00000386312.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152128Hom.: 0 Cov.: 32
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152128Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74318
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 17, 2023 | This variant, c.1651_1653del, results in the deletion of 1 amino acid(s) of the SCN1A protein (p.Ser551del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SCN1A-related conditions. This variant has been observed in at least one individual who was not affected with SCN1A-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 530498). 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. - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at