rs751294193
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PP2PP3BS1_SupportingBS2
The NM_006922.4(SCN3A):c.2021G>A(p.Gly674Asp) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000547 in 1,461,504 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. G674G) has been classified as Likely benign.
Frequency
Consequence
NM_006922.4 missense, splice_region
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 |
---|---|---|---|---|---|---|---|
SCN3A | NM_006922.4 | c.2021G>A | p.Gly674Asp | missense_variant, splice_region_variant | 14/28 | ENST00000283254.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN3A | ENST00000283254.12 | c.2021G>A | p.Gly674Asp | missense_variant, splice_region_variant | 14/28 | 1 | NM_006922.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 0AN: 152048Hom.: 0 Cov.: 33 FAILED QC
GnomAD3 exomes AF: 0.0000359 AC: 9AN: 250978Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135614
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461504Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 727048
GnomAD4 genome ? Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 152048Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74260
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 06, 2023 | An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. ClinVar contains an entry for this variant (Variation ID: 240708). This variant has not been reported in the literature in individuals affected with SCN3A-related conditions. This variant is present in population databases (rs751294193, gnomAD 0.02%). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 674 of the SCN3A protein (p.Gly674Asp). - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Aug 30, 2021 | - - |
Epilepsy, familial focal, with variable foci 4;C4693699:Developmental and epileptic encephalopathy, 62 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at