rs1553520319
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM1PM2PM5PP2PP3_ModeratePP5_Moderate
The NM_001165963.4(SCN1A):c.5171C>T(p.Ala1724Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1724P) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001165963.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCN1A | ENST00000674923.1 | c.5171C>T | p.Ala1724Val | missense_variant | 29/29 | NM_001165963.4 | ENSP00000501589.1 | |||
SCN1A | ENST00000303395.9 | c.5171C>T | p.Ala1724Val | missense_variant | 28/28 | 5 | ENSP00000303540.4 | |||
SCN1A | ENST00000375405.7 | c.5138C>T | p.Ala1713Val | missense_variant | 26/26 | 5 | ENSP00000364554.3 | |||
SCN1A | ENST00000409050.1 | c.5087C>T | p.Ala1696Val | missense_variant | 26/26 | 5 | ENSP00000386312.1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 15, 2021 | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Ala1724 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been observed in individuals with SCN1A-related conditions (PMID: 28012175, 30185235), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has been observed in individual(s) with SCN1A-related conditions (PMID: 31302675, 31273778). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 530420). This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with valine at codon 1724 of the SCN1A protein (p.Ala1724Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at