rs200821646
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP3BP6
The NM_001365536.1(SCN9A):c.1790G>A(p.Arg597Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000403 in 1,613,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R597G) has been classified as Uncertain significance.
Frequency
Consequence
NM_001365536.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN9A | NM_001365536.1 | c.1790G>A | p.Arg597Gln | missense_variant | 12/27 | ENST00000642356.2 | |
SCN1A-AS1 | NR_110260.1 | n.1029+7390C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN9A | ENST00000642356.2 | c.1790G>A | p.Arg597Gln | missense_variant | 12/27 | NM_001365536.1 | P1 | ||
SCN1A-AS1 | ENST00000651574.1 | n.1707+7390C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152166Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000161 AC: 4AN: 249074Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135116
GnomAD4 exome AF: 0.0000376 AC: 55AN: 1461694Hom.: 0 Cov.: 32 AF XY: 0.0000316 AC XY: 23AN XY: 727132
GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152166Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7AN XY: 74338
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 28, 2019 | The p.R597Q variant (also known as c.1790G>A), located in coding exon 11 of the SCN9A gene, results from a G to A substitution at nucleotide position 1790. The arginine at codon 597 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Generalized epilepsy with febrile seizures plus, type 7;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at