2-166045206-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 3P and 9B. PM5PP2BP4_StrongBP6BS2
The NM_001165963.4(SCN1A):c.1499G>A(p.Arg500Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,614,088 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. R500W) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001165963.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN1A | NM_001165963.4 | c.1499G>A | p.Arg500Gln | missense_variant | 13/29 | ENST00000674923.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN1A | ENST00000674923.1 | c.1499G>A | p.Arg500Gln | missense_variant | 13/29 | NM_001165963.4 | P4 | ||
SCN1A-AS1 | ENST00000651574.1 | n.487+9076C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152134Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000127 AC: 32AN: 251190Hom.: 0 AF XY: 0.000140 AC XY: 19AN XY: 135768
GnomAD4 exome AF: 0.0000315 AC: 46AN: 1461836Hom.: 0 Cov.: 32 AF XY: 0.0000220 AC XY: 16AN XY: 727226
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152252Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74436
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 01, 2021 | This variant is associated with the following publications: (PMID: 29314583) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 21, 2018 | - - |
Early infantile epileptic encephalopathy with suppression bursts Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at