chr2-165994164-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 4P and 7B. PM1PP2PP3BP4_ModerateBP6BS2
The NM_001165963.4(SCN1A):c.4834G>A(p.Val1612Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,610,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. V1612F) has been classified as Uncertain significance.
Frequency
Consequence
NM_001165963.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN1A | NM_001165963.4 | c.4834G>A | p.Val1612Ile | missense_variant | 28/29 | ENST00000674923.1 | |
LOC102724058 | NR_110598.1 | n.176-21449C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN1A | ENST00000674923.1 | c.4834G>A | p.Val1612Ile | missense_variant | 28/29 | NM_001165963.4 | P4 | ||
SCN1A-AS1 | ENST00000651574.1 | n.193-21449C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 151920Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000174 AC: 43AN: 247462Hom.: 0 AF XY: 0.000157 AC XY: 21AN XY: 133784
GnomAD4 exome AF: 0.0000267 AC: 39AN: 1458406Hom.: 0 Cov.: 30 AF XY: 0.0000248 AC XY: 18AN XY: 725438
GnomAD4 genome AF: 0.0000263 AC: 4AN: 151920Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2AN XY: 74202
ClinVar
Submissions by phenotype
Severe myoclonic epilepsy in infancy Benign:1Other:1
not provided, no classification provided | literature only | UniProtKB/Swiss-Prot | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 21, 2018 | The p.V1612I variant (also known as c.4834G>A), located in coding exon 25 of the SCN1A gene, results from a G to A substitution at nucleotide position 4834. The valine at codon 1612 is replaced by isoleucine, an amino acid with highly similar properties. This variant has been reported in three individuals with Dravet syndrome; in two of the individuals, it was inherited from parents (Depienne C et al. J. Med. Genet., 2009 Mar;46:183-91; Herini ES et al. Pediatr Int, 2010 Apr;52:234-9; Kwong AK et al. PLoS ONE, 2012 Jul;7:e41802). Based on data from gnomAD, the A allele has an overall frequency of approximately 0.02% (46/273258) total alleles studied. The highest observed frequency was 0.24% (44/18572) of East Asian alleles. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is conflicting at this time, the clinical significance of this alteration remains unclear. - |
Early infantile epileptic encephalopathy with suppression bursts Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 08, 2023 | - - |
Secondary microcephaly;C0543888:Epileptic encephalopathy;C0557874:Global developmental delay;C0684276:Hypsarrhythmia;C1836806:Mild microcephaly;C1858120:Generalized hypotonia;C2081594:Plagiocephaly;C3665347:Visual impairment;C3887898:Infantile spasms;C4021160:Posterior plagiocephaly;C4048268:Cerebral visual impairment Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Personalized Medicine, Children's Hospital Los Angeles | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at