chr2-166198690-G-C
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001365536.1(SCN9A):āc.5949C>Gā(p.Ser1983Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000565 in 1,593,706 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. S1983I) has been classified as Uncertain significance.
Frequency
Consequence
NM_001365536.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN9A | NM_001365536.1 | c.5949C>G | p.Ser1983Arg | missense_variant | 27/27 | ENST00000642356.2 | |
SCN1A-AS1 | NR_110260.1 | n.432-949G>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN9A | ENST00000642356.2 | c.5949C>G | p.Ser1983Arg | missense_variant | 27/27 | NM_001365536.1 | P1 | ||
SCN1A-AS1 | ENST00000651574.1 | n.1110-949G>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.000257 AC: 39AN: 151992Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000781 AC: 18AN: 230498Hom.: 0 AF XY: 0.0000562 AC XY: 7AN XY: 124504
GnomAD4 exome AF: 0.0000277 AC: 40AN: 1441596Hom.: 0 Cov.: 31 AF XY: 0.0000238 AC XY: 17AN XY: 715484
GnomAD4 genome AF: 0.000329 AC: 50AN: 152110Hom.: 2 Cov.: 32 AF XY: 0.000390 AC XY: 29AN XY: 74364
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 28, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 29, 2020 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
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 16, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at