chr2-165090197-G-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong
The NM_006922.4(SCN3A):c.5956C>A(p.Pro1986Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,601,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_006922.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN3A | NM_006922.4 | c.5956C>A | p.Pro1986Thr | missense_variant | 28/28 | ENST00000283254.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN3A | ENST00000283254.12 | c.5956C>A | p.Pro1986Thr | missense_variant | 28/28 | 1 | NM_006922.4 | P1 | |
ENST00000638199.1 | n.1144-923G>T | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000659 AC: 1AN: 151746Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000138 AC: 2AN: 1450156Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1AN XY: 720440
GnomAD4 genome ? AF: 0.00000659 AC: 1AN: 151746Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74094
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 04, 2019 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SCN3A-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with threonine at codon 1986 of the SCN3A protein (p.Pro1986Thr). The proline residue is moderately conserved and there is a small physicochemical difference between proline and threonine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at