rs199583108
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001365536.1(SCN9A):āc.3209T>Cā(p.Leu1070Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,613,306 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. L1070L) has been classified as Likely benign.
Frequency
Consequence
NM_001365536.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN9A | NM_001365536.1 | c.3209T>C | p.Leu1070Ser | missense_variant | 17/27 | ENST00000642356.2 | |
SCN1A-AS1 | NR_110260.1 | n.870-4547A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN9A | ENST00000642356.2 | c.3209T>C | p.Leu1070Ser | missense_variant | 17/27 | NM_001365536.1 | P1 | ||
SCN1A-AS1 | ENST00000651574.1 | n.1548-4547A>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151982Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000804 AC: 2AN: 248720Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 134934
GnomAD4 exome AF: 0.0000356 AC: 52AN: 1461324Hom.: 0 Cov.: 32 AF XY: 0.0000261 AC XY: 19AN XY: 726934
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151982Hom.: 0 Cov.: 31 AF XY: 0.0000270 AC XY: 2AN XY: 74180
ClinVar
Submissions by phenotype
Generalized epilepsy with febrile seizures plus, type 7;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 23, 2023 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SCN9A protein function. ClinVar contains an entry for this variant (Variation ID: 566344). This variant has not been reported in the literature in individuals affected with SCN9A-related conditions. This variant is present in population databases (rs199583108, gnomAD 0.002%). This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1059 of the SCN9A protein (p.Leu1059Ser). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at