rs915676341
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 3P and 6B. PM1PP2BP4_ModerateBS2
The NM_001165963.4(SCN1A):c.5813C>T(p.Ala1938Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,613,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1938D) has been classified as Uncertain significance.
Frequency
Consequence
NM_001165963.4 missense
Scores
Clinical Significance
Conservation
Publications
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ACMG classification
Our verdict: Likely_benign. The variant received -3 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCN1A | ENST00000674923.1 | c.5813C>T | p.Ala1938Val | missense_variant | Exon 29 of 29 | NM_001165963.4 | ENSP00000501589.1 | |||
SCN1A | ENST00000303395.9 | c.5813C>T | p.Ala1938Val | missense_variant | Exon 28 of 28 | 5 | ENSP00000303540.4 | |||
SCN1A | ENST00000375405.7 | c.5780C>T | p.Ala1927Val | missense_variant | Exon 26 of 26 | 5 | ENSP00000364554.3 | |||
SCN1A | ENST00000409050.2 | c.5729C>T | p.Ala1910Val | missense_variant | Exon 28 of 28 | 5 | ENSP00000386312.1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152072Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.00000798 AC: 2AN: 250608 AF XY: 0.0000148 show subpopulations
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461666Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727132 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152072Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74278 show subpopulations
ClinVar
Submissions by phenotype
Generalized epilepsy with febrile seizures plus, type 2 Pathogenic:1
- -
Severe myoclonic epilepsy in infancy Pathogenic:1
- -
Developmental and epileptic encephalopathy Benign:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at